Toll-like receptor 4 (TLR4) and TLR2 were shown to be activated by saturated fatty acids (SFAs) but inhibited by docosahexaenoic acid (DHA). However, one report suggested that SFA-induced TLR activation in cell culture systems is due to contaminants in BSA used for solubilizing fatty acids. This report raised doubt about proinflammatory effects of SFAs. Our studies herein demonstrate that sodium palmitate (C16:0) or laurate (C12:0) without BSA solubilization induced phosphorylation of inhibitor of nuclear factor-κB α, c-Jun N-terminal kinase (JNK), p44/42 mitogen-activated-kinase (ERK), and nuclear factor-κB subunit p65, and TLR target gene expression in THP1 monocytes or RAW264.7 macrophages, respectively, when cultured in low FBS (0.25%) medium. C12:0 induced NFκB activation through TLR2 dimerized with TLR1 or TLR6, and through TLR4. Because BSA was not used in these experiments, contaminants in BSA have no relevance. Unlike in suspension cells (THP-1), BSA-solubilized C16:0 instead of sodium C16:0 is required to induce TLR target gene expression in adherent cells (RAW264.7). C16:0-BSA transactivated TLR2 dimerized with TLR1 or TLR6 and through TLR4 as seen with C12:0. These results and additional studies with the LPS sequester polymixin B and in MyD88−/− macrophages indicated that SFA-induced activation of TLR2 or TLR4 is a fatty acid-specific effect, but not due to contaminants in BSA or fatty acid preparations. Toll-like receptor 4 (TLR4) and TLR2 were shown to be activated by saturated fatty acids (SFAs) but inhibited by docosahexaenoic acid (DHA). However, one report suggested that SFA-induced TLR activation in cell culture systems is due to contaminants in BSA used for solubilizing fatty acids. This report raised doubt about proinflammatory effects of SFAs. Our studies herein demonstrate that sodium palmitate (C16:0) or laurate (C12:0) without BSA solubilization induced phosphorylation of inhibitor of nuclear factor-κB α, c-Jun N-terminal kinase (JNK), p44/42 mitogen-activated-kinase (ERK), and nuclear factor-κB subunit p65, and TLR target gene expression in THP1 monocytes or RAW264.7 macrophages, respectively, when cultured in low FBS (0.25%) medium. C12:0 induced NFκB activation through TLR2 dimerized with TLR1 or TLR6, and through TLR4. Because BSA was not used in these experiments, contaminants in BSA have no relevance. Unlike in suspension cells (THP-1), BSA-solubilized C16:0 instead of sodium C16:0 is required to induce TLR target gene expression in adherent cells (RAW264.7). C16:0-BSA transactivated TLR2 dimerized with TLR1 or TLR6 and through TLR4 as seen with C12:0. These results and additional studies with the LPS sequester polymixin B and in MyD88−/− macrophages indicated that SFA-induced activation of TLR2 or TLR4 is a fatty acid-specific effect, but not due to contaminants in BSA or fatty acid preparations. endogenous damage associated molecular pattern docosahexaenoic acid p44/42 mitogen-activated-kinase inhibitor of nuclear factor-κB interleukin c-Jun N-terminal kinase Limulus Amebocyte Lysate lipopolysaccharide muramyldipeptide MurNAc-L-Ala-D-isoGln nuclear factor-κB nucleotide-binding oligomerization domain family pathogen-associated molecular pattern pattern recognition receptor reactive oxygen species saturated fatty acid Toll-like receptor Pattern recognition receptors (PRRs), including Toll-like receptors (TLRs) and nucleotide-binding oligomerization domain protein (NOD) like receptors detect invading pathogens by recognizing conserved pathogen-associated molecular patterns (PAMPs) and activate innate immune responses for host defense. However, PRRs can be activated by a wide variety of endogenous damage associated molecular patterns (DAMPs) derived from tissue injury or stress and induce sterile inflammation to initiate wound healing processes. Emerging evidence suggests that PRRs can also sense metabolic disturbance and link immune responses to metabolic homeostasis (1Hotamisligil G.S. Erbay E. Nutrient sensing and inflammation in metabolic diseases.Nat. Rev. Immunol. 2008; 8: 923-934Crossref PubMed Scopus (778) Google Scholar, 2Schroder K. Zhou R. Tschopp J. The NLRP3 inflammasome: a sensor for metabolic danger?.Science. 2010; 327: 296-300Crossref PubMed Scopus (847) Google Scholar). Such a functional diversity of PRRs may be achieved by their ability to recognize a wide variety of structurally unrelated molecules. However, such a broad specificity of PRRs in recognizing agonists can make them susceptible to dysregulation leading to development of chronic inflammation, which in turn can promote development and progression of many chronic diseases including atherosclerosis, insulin resistance, Alzheimer's disease, and cancer. Recent studies revealed that dietary components and metabolic intermediates can alter the activity and expression of PRRs, suggesting that PRR-mediated inflammation and its functional consequence are dynamically modulated by what we eat (3Lee J.Y. Zhao L. Hwang D.H. Modulation of pattern recognition receptor-mediated inflammation and risk of chronic diseases by dietary fatty acids.Nutr. Rev. 2010; 68: 38-61Crossref PubMed Scopus (117) Google Scholar, 4Zhao L. Lee J.Y. Hwang D.H. Inhibition of pattern recognition receptor-mediated inflammation by bioactive phytochemicals.Nutr. Rev. 2011; 69: 310-320Crossref PubMed Scopus (85) Google Scholar). High saturated fat diets have been used for diet-induced obesity and insulin resistance in many animal studies. Both in vitro and in vivo studies suggest that saturated fatty acids (SFAs) can activate proinflammatory signaling pathways leading to insulin resistance (5Glass C.K. Olefsky J.M. Inflammation and lipid signaling in the etiology of insulin resistance.Cell Metab. 2012; 15: 635-645Abstract Full Text Full Text PDF PubMed Scopus (585) Google Scholar). The molecular mechanism by which SFAs activate proinflammatory signaling pathways remains obscure. Our previous studies revealed that SFAs activate but n-3 PUFA docosahexaenoic acid (DHA) inhibits TLR4- and TLR2-mediated signaling pathways leading to expression of proinflammatory marker gene products (6Lee J.Y. Sohn K.H. Rhee S.H. Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4.J. Biol. Chem. 2001; 276: 16683-16689Abstract Full Text Full Text PDF PubMed Scopus (990) Google Scholar–9Lee J.Y. Plakidas A. Lee W.H. Heikkinen A. Chanmugam P. Bray G. Hwang D.H. Differential modulation of Toll-like receptors by fatty acids: preferential inhibition by n-3 polyunsaturated fatty acids.J. Lipid Res. 2003; 44: 479-486Abstract Full Text Full Text PDF PubMed Scopus (460) Google Scholar). Numerous studies with cells in culture and in animal models of mutated or deleted TLR4 or TLR2 subsequently demonstrated that SFAs indeed can activate TLR4- and TLR2-mediated proinflammatory signaling pathways and consequently, increase risk of insulin resistance (10Shi H. Kokoeva M.V. Inouye K. Tzameli I. Yin H. Flier J.S. TLR4 links innate immunity and fatty acid-induced insulin resistance.J. Clin. Invest. 2006; 116: 3015-3025Crossref PubMed Scopus (2681) Google Scholar–19Davis J.E. Braucher D.R. Walker-Daniels J. Spurlock M.E. Absence of Tlr2 protects against high-fat diet-induced inflammation and results in greater insulin-stimulated glucose transport in cultured adipocytes.J. Nutr. Biochem. 2011; 22: 136-141Crossref PubMed Scopus (79) Google Scholar). However, one report (20Erridge C. Samani N.J. Saturated fatty acids do not directly stimulate Toll-like receptor signaling.Arterioscler. Thromb. Vasc. Biol. 2009; 29: 1944-1949Crossref PubMed Scopus (215) Google Scholar) suggested that SFA-induced TLR activation is due to contaminants in BSA used for solubilizing fatty acids. This report casted doubt upon the proinflammatory effects of SFAs. TLRs are activated by various microbial components (i.e., endotoxins) that are ubiquitously present in our environment. Therefore, potential contamination of microbial components in reagents used for in vitro and in vivo studies is not a trivial technical issue for investigations focusing on the of endogenous in TLRs and Such is the are in This issue was in the the activation of TLR4 by as a protein is a of or due to contaminants K. H. protein is a endogenous of the Immunol. PubMed Scopus Google Scholar, protein not induce the of from Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar). is not for the of can also be used to detect and agonists for Therefore, we used to potential contamination of TLR agonists in of evidence are that the activation of proinflammatory signaling pathways by SFAs is a fatty acid-specific and not due to contaminants in the of cells to fatty acids revealed that the of cells to TLR agonists is on the of reactive oxygen species in cell culture and were from and of polymixin and for were from for c-Jun N-terminal kinase p44/42 mitogen-activated-kinase of nuclear B B nuclear B and B were from B was from immune was a as were as FBS and and FBS from FBS from FBS from and FBS from BSA was from laurate was from acid sodium palmitate sodium and BSA and were from was from TLR4 inhibitor was from cell from macrophages by of and by were cultured in FBS and cells cell were cultured in and The macrophages were macrophages from with A. H. E. and activate the through Immunol. 2008; PubMed Scopus Google Scholar). cell were in a and were from of was by was by was from Lee of The from these expression was in for the were to the cells were of and the with of and or and or and in to and expression of was used in to the of and expression for as the cells were in for by with fatty acids in the low medium. The cells were and were from the the and to the activity was by activity to in of the was acid (C16:0) is and to be with BSA to The solubilization was as G. for but not in the of insulin by saturated fatty acids.J. Biol. Chem. 2003; Full Text Full Text PDF PubMed Scopus Google Scholar) with C16:0 was in or with BSA in a in or medium. The was in a for by on a in for The C16:0 was through a of sodium was in of sodium was in in a and to sodium was to and cells were to indicated in of sodium was in with in and and cells were of The the cells were in for and with fatty acids in the medium. cells were in and in for The cells were with fatty acids in the low medium. the the were The cells were with and by in cell sodium and The were by and to by of the to The was in and The was with for or by with for The were by the reagents by to were for and interleukin in the cell culture a and respectively, and a the RAW264.7 cells were of in medium. The the cells were in for by with or BSA-solubilized C16:0 for The cells were with and with for The cells were with and by in The of were from the cells by with a a The of were also by cells were a in a of in The cells were for and with in for with the cells were with or BSA-solubilized C16:0 for in The cells were with in for and with The were on was with a with The Amebocyte were a the was with reagents and for The was The were also a the of were with and for of was to of the and for or low The were by of the The were by a the The of the were from the the by the of the was from the and as were by a Our previous studies demonstrated that sodium laurate (C12:0) BSA PRRs J.Y. Zhao L. R. L. Lee W.H. Hwang D.H. Saturated fatty acid but polyunsaturated fatty acid inhibits Toll-like receptor dimerized with Toll-like receptor or Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, L. Lee J.Y. K. Hwang D.H. Differential modulation of signaling pathways by fatty acids in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). Therefore, potential contamination of agonists in BSA was not with our previous of cells with sodium laurate (C12:0) to of and expression However, acid (C16:0) is in and to be with BSA to expression of target is to contaminants in we cells with BSA or BSA-solubilized C16:0 to sodium C16:0-BSA induced and expression BSA used to C16:0 no we C12:0 or expression of or is due to contamination of LPS in BSA or fatty acid preparations. The LPS polymixin B not C12:0 or and expression that the effects of the SFAs are not due to LPS contamination in BSA or fatty acid B not sodium laurate or acid expression that the of expression by these fatty acids is not due to LPS contamination in the fatty acid or BSA preparations. cells were in for and with polymixin B for by with or of BSA in the for The protein were with or by were for by polymixin from no B and Samani (20Erridge C. Samani N.J. Saturated fatty acids do not directly stimulate Toll-like receptor signaling.Arterioscler. Thromb. Vasc. Biol. 2009; 29: 1944-1949Crossref PubMed Scopus (215) Google Scholar) suggested that SFA-induced expression in cells is due to contaminants present in BSA or fatty acid that can activate that is the or or expression be in macrophages TLR2 signaling Therefore, we or C16:0-BSA induced or expression is in The results that C12:0 or C16:0-BSA induced and expression in macrophages the that the of or expression by C12:0 or C16:0-BSA is due to contaminants in BSA or fatty acid that can activate TLR2 or TLRs or studies have shown that SFAs can activate and in macrophages (6Lee J.Y. Sohn K.H. Rhee S.H. Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4.J. Biol. Chem. 2001; 276: 16683-16689Abstract Full Text Full Text PDF PubMed Scopus (990) Google Scholar, J.Y. Zhao L. R. L. Lee W.H. Hwang D.H. Saturated fatty acid but polyunsaturated fatty acid inhibits Toll-like receptor dimerized with Toll-like receptor or Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, H. Kokoeva M.V. Inouye K. Tzameli I. Yin H. Flier J.S. TLR4 links innate immunity and fatty acid-induced insulin resistance.J. Clin. Invest. 2006; 116: 3015-3025Crossref PubMed Scopus (2681) Google Scholar, D. A. R. C.K. Olefsky J.M. of macrophages tissue and is activated by fatty acids Toll-like receptors and 4 and Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar, L. Lee J.Y. K. Hwang D.H. Differential modulation of signaling pathways by fatty acids in Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). TLR4 and and is not the of SFAs induce the expression of or in cells as shown in evidence that proinflammatory effects of SFAs are not due to the potential contaminants in the reagents in in vitro systems is that SFAs activate proinflammatory signaling n-3 fatty acid SFA-induced activation of proinflammatory signaling pathways (3Lee J.Y. Zhao L. Hwang D.H. Modulation of pattern recognition receptor-mediated inflammation and risk of chronic diseases by dietary fatty acids.Nutr. Rev. 2010; 68: 38-61Crossref PubMed Scopus (117) Google Scholar, J.Y. Sohn K.H. Rhee S.H. Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4.J. Biol. Chem. 2001; 276: 16683-16689Abstract Full Text Full Text PDF PubMed Scopus (990) Google K. Hwang D.H. acids Toll-like receptor 4 activation through of receptor and lipid in a reactive oxygen Biol. Chem. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar). C12:0 induced phosphorylation of and but inhibited phosphorylation and expression cells were with fatty acids in the of polymixin B C12:0 or C16:0-BSA induced and expression effects of LPS and contaminants that can activate TLRs are be that we have BSA for the of potential contaminants that can induce the expression of TLR or target gene products in RAW264.7 BSA induced the expression of TLR target gene suggesting the of contaminants that can activate TLR or PRRs in these BSA preparations. and which induced expression in RAW264.7 cells in the of polymixin B not induce expression in cells suggesting that the contaminants in these BSA are that can activate TLR2 or proinflammatory these results demonstrate that fatty acid-induced or expression is not due to LPS or contaminants that can activate TLR2 or TLRs in BSA or fatty acid preparations. that these BSA of these BSA the one from not of and expression also that BSA of Therefore, BSA was used the studies. the of RAW264.7 cells to SFAs with the of FBS This in the of RAW264.7 cells to C12:0 was not with the fatty acid of in FBS not laurate (C12:0) without BSA solubilization activated the signaling pathways of TLRs in adherent leading to phosphorylation of and phosphorylation was by leading to of expression of cells suspension cell with sodium palmitate (C16:0) without BSA solubilization activated the signaling pathways of leading to phosphorylation of B and B subunit The activation of the TLR pathways by C16:0 to expression of to expression was also by polymixin B no C16:0-BSA but not BSA also induced phosphorylation and expression in cells expression induced by C16:0-BSA was inhibited by but was not by polymixin B Because BSA was not used in studies with sodium laurate and sodium potential contaminants in BSA that can activate PRRs were not C12:0 transactivated B mediated through TLR2 dimerized with TLR1 or TLR6, or through TLR4 C16:0-BSA also induced B activation mediated through these TLRs these results that SFA-induced activation of signaling pathways of TLR4 and TLR2 is the of SFAs and not due to potential contaminants in fatty acid or BSA laurate (C12:0) or acid induced B activation through TLR2 dimerized with TLR1 or TLR6 and through TLR4. cells were cultured in and with TLR2 and TLR1 TLR2 and TLR6 TLR4 and in to and expression the cells were in for and with C12:0 or C16:0-BSA for The cell were for and are as LPS was used as from or from BSA our previous studies that SFAs activate TLR2 and cells were cultured in the medium. we the of cells to C12:0 or TLR agonists is by in the culture The of cells to or TLR agonists a TLR4 a TLR2 was when the cells were cultured in the (0.25%) with the cells cultured in FBS The of expression by C12:0 was in the cells cultured in the with FBS results were with C16:0-BSA The activation of expression by or C16:0-BSA was also in cells cultured in the (0.25%) with cells cultured in the be that the results by and Samani (20Erridge C. Samani N.J. Saturated fatty acids do not directly stimulate Toll-like receptor signaling.Arterioscler. Thromb. Vasc. Biol. 2009; 29: 1944-1949Crossref PubMed Scopus (215) Google Scholar) that sodium laurate not induce expression or B were in cells cultured in the with laurate or TLR and reactive oxygen species and phosphorylation of and were in the culture with low FBS (0.25%) with with FBS cells were in for and with C12:0 or C16:0-BSA for in the or cultured in and with C12:0 or C16:0-BSA for The protein were for and by The culture from and C16:0-BSA were for by cells were cultured in or FBS for and with or C16:0-BSA for by for were by as in of the by the in as of from the of FBS for and C16:0-BSA cells were in for and with C12:0 for indicated or cultured in and with C12:0 for the The protein were for and by what to the of cells to fatty acids in the medium. The of been shown to be by in or cells in culture H. of reactive oxygen species induced by in Res. PubMed Scopus Google I. H. J. of Chem. 2011; PubMed Scopus Google Scholar). activation of TLR4 of the receptor lipid in K. A. stress by Toll-like receptor 4 to the in 2006; PubMed Scopus Google Scholar, K. A. inhibits TLR signaling pathways by of TLRs to lipid 2006; PubMed Scopus Google Scholar). Our previous studies demonstrated that C12:0 and of TLR4 lipid in K. Hwang D.H. acids Toll-like receptor 4 activation through of receptor and lipid in a reactive oxygen Biol. Chem. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar). of TLR2 was also shown to stimulate the activity of K.H. Lee Lee with TLR2 is required for innate immune responses to Immunol. 2009; PubMed Scopus Google Scholar, Lee acid expression the and in Immunol. 2008; PubMed Scopus Google Scholar). these results suggest that the of cells to TLR4 agonists in on of cells in Therefore, we the in the cells cultured in the with or low (0.25%) FBS shown in and in or cells was by the culture with FBS with that with suggesting that the effects of SFAs. phosphorylation of and was the cells were cultured in low FBS (0.25%) with FBS These results suggest that low in culture in the of cells to LPS or SFAs in signaling with of RAW264.7 cells with sodium C12:0 or C16:0-BSA in the to inhibitor of the phosphorylation of and and the expression of and induced by C12:0 or C16:0-BSA in the these results demonstrate that in cells in culture is one of the that can the of the cells to SFAs. Our results demonstrate that SFAs without to BSA can activate proinflammatory signaling pathways in macrophages and monocytes in a low culture medium. However, inhibits saturated fatty acid-induced activation of signaling These results that SFA-induced activation of signaling pathways and target gene expression is not due to contaminants in BSA or fatty acid preparations. The results from also that the fatty acids and reagents used in these studies or of that sodium palmitate and acid used in these of and which is to LPS and respectively, as from the LPS However, in sodium palmitate and acid as by not a pattern suggesting that for acid may by be that a of the for or the to M.E. with the and to of 22: Scholar). Therefore, we have to and contaminants in our reagents that can activate TLR2 or TLR4. cells in the of polymixin effects of and potential contaminants that can activate TLR2 and TLRs are Therefore, the activation of TLR2 or TLR4 by SFAs is due to contaminants that can activate TLR2 or the SFAs not be to induce the expression of TLR target gene products in cells in the of polymixin The that the SFAs induce the expression of the TLR target gene products that the activation of TLR2 or TLR4 by the SFAs is not due to the of potential contaminants that can activate TLR2 or TLR4. we the of in palmitate as by as these of in palmitate for the expression of or induced by inhibited or SFA-induced TLR target gene expression C12:0 or C16:0 effects on TLR activation in our studies these fatty acids are in in the is that SFAs are with that can stimulate TLR is with that can TLR these results the that the effects of SFAs may be due to contaminants in fatty acid preparations. a inhibitor of TLR4 and and suggesting that activation of and expression is in mediated through TLR4 signaling Our previous studies also that C12:0 and of TLR4 lipid K. Hwang D.H. acids Toll-like receptor 4 activation through of receptor and lipid in a reactive oxygen Biol. Chem. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar). The of cells to SFAs is in the culture with low FBS (0.25%) with the culture with which is with by the cells cultured in the medium. These results about the activation of signaling pathways induced by SFAs and suggest that that can the of cells to SFAs in signaling pathways and its functional SFAs can activate TLR2 and TLR4 is receptor of the receptor lipid and of the signaling are the potential through which fatty acids can activation of these The Lipid in LPS is by SFAs of Rev. Biochem. PubMed Scopus Google Scholar). of these SFAs from Lipid results in of activity of by a PubMed Scopus Google Scholar). Lipid by unsaturated fatty acids instead of SFAs is and as against the responses to LPS in a cell without LPS by a PubMed Scopus Google K. R. lipid from the lipopolysaccharide of is in PubMed Google Scholar). that activate TLR2 are also by SFAs. These results suggest that the fatty acids in lipid or a in receptor activation for TLR2 and TLR4. The for revealed that of fatty in LPS are the in D.H. Lee H. Lee The of lipopolysaccharide recognition by the 2009; PubMed Scopus Google Scholar). of LPS to with TLR4 through and mediated by the fatty and in Lipid is fatty acids the of Lipid the SFAs in Lipid can with the of and of TLR4 with or The for revealed that fatty of are the in the fatty is a in TLR1 J.Y. Lee M.E. Lee H. Lee of the induced by of a Full Text Full Text PDF PubMed Scopus Google Scholar). of fatty of TLR2 of is saturated fatty acids the fatty acids in the can with the in TLR2 or TLR1 and promote the of the receptors or the of the receptors with the through TLR2 and TLR1 or TLR6 can in a when are A. L. A. The for pattern recognition of pathogens by the innate immune is by PubMed Scopus Google Scholar). was shown that acid can activate TLR4 and TLR2 dimerized with TLR1 or TLR6 but no TLRs (6Lee J.Y. Sohn K.H. Rhee S.H. Hwang D. Saturated fatty acids, but not unsaturated fatty acids, induce the expression of cyclooxygenase-2 mediated through Toll-like receptor 4.J. Biol. Chem. 2001; 276: 16683-16689Abstract Full Text Full Text PDF PubMed Scopus (990) Google Scholar, J.Y. Zhao L. R. L. Lee W.H. Hwang D.H. Saturated fatty acid but polyunsaturated fatty acid inhibits Toll-like receptor dimerized with Toll-like receptor or Biol. Chem. Full Text Full Text PDF PubMed Scopus Google Scholar). The and indicated the of the lipid or in or of and TLR6 but not in TLRs J.Y. Lee of the Toll-like receptor Rev. Biochem. 2011; PubMed Scopus Google Scholar). for TLRs TLR4 and TLR2 are to be by SFAs. the molecular LPS or and TLR4 or respectively, been revealed receptors without potential activity of various endogenous fatty remains to be of TLR4 of the receptor lipid signaling such as and for the activation of signaling pathways K. Hwang D.H. acids Toll-like receptor 4 activation through of receptor and lipid in a reactive oxygen Biol. Chem. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar, K. A. stress by Toll-like receptor 4 to the in 2006; PubMed Scopus Google Scholar, K. A. inhibits TLR signaling pathways by of TLRs to lipid 2006; PubMed Scopus Google Scholar). Lipid are of which as signaling to and signaling to promote the of to signaling Lipid have a lipid that is in and The in lipid are by SFAs in which are by suggesting that saturated fatty lipid Both TLR4 and TLR2 LPS and respectively, are by SFAs. for the of lipid suggests that of with for lipid can increase the and of lipid Lipid and 2006; PubMed Scopus Google Scholar). was shown that acid but n-3 PUFA inhibits and of TLR4 lipid in macrophages K. Hwang D.H. acids Toll-like receptor 4 activation through of receptor and lipid in a reactive oxygen Biol. Chem. 2009; Full Text Full Text PDF PubMed Scopus Google Scholar). mechanism by which SFAs activate TLR2 and TLR4 of endogenous signaling or of that can with However, no evidence been to The results demonstrate that SFA-induced activation of TLR2 and TLR4 is fatty acid effects but not due to contaminants in TLRs are not in host but also wound healing and metabolic disturbance to immune Such of TLRs can be by recognizing a variety of endogenous molecules. the molecular TLR4 or TLR2 and their (i.e., LPS and been revealed by studies receptors without the potential activity of a variety of endogenous fatty remains to be of the mechanism by which such endogenous activate signaling pathways our of sterile inflammation is associated with the development and progression of many chronic