Abstract
There are limitations in the current classification of danger-associated molecular patterns (DAMP) receptors. To overcome these limitations, we propose a new paradigm by using endogenous metabolites lysophospholipids (LPLs) as a prototype. By utilizing a data mining method we pioneered, we made the following findings: (1) endogenous metabolites such as LPLs at basal level have physiological functions; (2) under sterile inflammation, expression of some LPLs is elevated. These LPLs act as conditional DAMPs or anti-inflammatory homeostasis-associated molecular pattern molecules (HAMPs) for regulating the progression of inflammation or inhibition of inflammation, respectively; (3) receptors for conditional DAMPs and HAMPs are differentially expressed in human and mouse tissues; and (4) complex signaling mechanism exists between pro-inflammatory mediators and classical DAMPs that regulate the expression of conditional DAMPs and HAMPs. This novel insight will facilitate identification of novel conditional DAMPs and HAMPs, thus promote development of new therapeutic targets to treat inflammatory disorders.
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Abbreviations
- PAMP:
-
Pathogen-associated molecular patterns
- DAMP:
-
Danger-associated molecular patterns
- TLR:
-
Toll-like receptors
- NLR:
-
NOD-like receptors
- NOD:
-
Nucleotide binding and oligomerization domain
- RIG-I:
-
Retinoid acid inducible gene I
- AIM2:
-
Absent in melanoma 2
- RAGE:
-
Receptor for advanced glycation end product
- HMGB1:
-
High mobility group box 1
- IL:
-
Interleukin
- TGF-β:
-
Transforming growth factor-β
- LPLs:
-
Lysophospholipids
- GPCRs:
-
G-protein coupled receptors
- LPA:
-
Lysophosphatidic acid
- LPC:
-
Lysophosphatidylcholine
- LPE:
-
Lysophosphatidylenthaolamine
- LPG:
-
Lysophosphoglycan
- LPI:
-
Lysophosphatidylinositol
- LysoPS:
-
Lysophosphatidylserine
- CAD:
-
Coronary artery disease
- SPM:
-
Specialized pro-resolving mediators
- EST:
-
Expressed sequence tags
- NIH:
-
National Institute of Health
- NCBI:
-
National Center of Biotechnology Information
- ROCK:
-
Rho-associated kinase
- DAG:
-
Diacylglycerol
- IP3:
-
Inositol 1,4,5-triphosphate
- MAPK:
-
Mitogen-activated protein kinase
- AC:
-
Adenylate cyclase
- PI3K:
-
Phosphoinositide-3-kinase
- PKC:
-
Protein kinase C
- SRF:
-
Serum response factor
- SPC:
-
Sphingosylphosphorylcholine
- IFN-γ:
-
Interferon-γ
References
Yang, X. F., Yin, Y., & Wang, H. (2008). Vascular inflammation and atherogenesis are activated via receptors for PAMPs and suppressed by regulatory T cells. Drug Discovery Today. Therapeutic Strategies, 5(2), 125–142. doi:10.1016/j.ddstr.2008.11.003.
Yin, Y., Yan, Y., Jiang, X., Mai, J., Chen, N. C., Wang, H., et al. (2009). Inflammasomes are differentially expressed in cardiovascular and other tissues. International Journal of Immunopathology and Pharmacology, 22(2), 311–322.
Yin, Y., Pastrana, J. L., Li, X., Huang, X., Mallilankaraman, K., Choi, E. T., et al. (2013). Inflammasomes: sensors of metabolic stresses for vascular inflammation. [Research Support, N.I.H., Extramural]. Frontiers in Bioscience, 18, 638–649.
Venereau, E., Ceriotti, C., & Bianchi, M. E. (2015). DAMPs from cell death to new life. [Review]. Frontiers in Immunology, 6, 422. doi:10.3389/fimmu.2015.00422.
Matzinger, P. (2002). The danger model: a renewed sense of self. Science, 296(5566), 301–305. doi:10.1126/science.1071059.
Medzhitov, R., & Horng, T. (2009). Transcriptional control of the inflammatory response. [Research Support, Non-U.S. Gov’t Review]. Nature Reviews Immunology, 9(10), 692–703. doi:10.1038/nri2634.
Rosin, D. L., & Okusa, M. D. (2011). Dangers within: DAMP responses to damage and cell death in kidney disease. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Journal of the American Society of Nephrology, 22(3), 416–425. doi:10.1681/ASN.2010040430.
Kuhn, T. S. (1996). The structure of scientific revolutions (3rd ed.). Chicago: University of Chicago Press.
Chen, L., & Flies, D. B. (2013). Molecular mechanisms of T cell co-stimulation and co-inhibition. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Nature Reviews Immunology, 13(4), 227–242. doi:10.1038/nri3405.
Fathman, C. G., & Lineberry, N. B. (2007). Molecular mechanisms of CD4+ T-cell anergy. [Research Support, N.I.H., Extramural Review]. Nature Reviews Immunology, 7(8), 599–609. doi:10.1038/nri2131.
Yang, W. Y., Shao, Y., Lopez-Pastrana, J., Mai, J., Wang, H., & Yang, X.-f. (2015). Pathological conditions re-shape physiological Tregs into pathological Tregs. Burns & Trauma, 3, 1–11. doi:10.1186/s41038-015-0001-0.
Vignali, D. A., & Kuchroo, V. K. (2012). IL-12 family cytokines: immunological playmakers. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Nature Immunology, 13(8), 722–728. doi:10.1038/ni.2366.
Li, X., Mai, J., Virtue, A., Yin, Y., Gong, R., Sha, X., et al. (2012). IL-35 is a novel responsive anti-inflammatory cytokine—a new system of categorizing anti-inflammatory cytokines. [Research Support, N.I.H., Extramural]. PLoS ONE, 7(3), e33628. doi:10.1371/journal.pone.0033628.
Sha, X., Meng, S., Li, X., Xi, H., Maddaloni, M., Pascual, D. W., et al. (2015). Interleukin-35 inhibits endothelial cell activation by suppressing MAPK-AP-1 pathway. [Research Support, N.I.H., Extramural]. Journal of Biological Chemistry, 290(31), 19307–19318. doi:10.1074/jbc.M115.663286.
Garlanda, C., Dinarello, C. A., & Mantovani, A. (2013). The interleukin-1 family: back to the future. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Immunity, 39(6), 1003–1018. doi:10.1016/j.immuni.2013.11.010.
Ng, B., Yang, F., Huston, D. P., Yan, Y., Yang, Y., Xiong, Z., et al. (2004). Increased noncanonical splicing of autoantigen transcripts provides the structural basis for expression of untolerized epitopes. Journal of Allergy and Clinical Immunology, 114(6), 1463–1470.
Li, Y. F., Li, R. S., Samuel, S. B., Cueto, R., Li, X. Y., Wang, H., et al. (2016). Lysophospholipids and their G protein-coupled receptors in atherosclerosis. Frontiers in Bioscience (Landmark Edition), 21, 70–88.
Smyth, S. S., Mueller, P., Yang, F., Brandon, J. A., & Morris, A. J. (2014). Arguing the case for the autotaxin-lysophosphatidic acid-lipid phosphate phosphatase 3-signaling nexus in the development and complications of atherosclerosis. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Arteriosclerosis, Thrombosis, and Vascular Biology, 34(3), 479–486. doi:10.1161/ATVBAHA.113.302737.
Abdel-Latif, A., Heron, P. M., Morris, A. J., & Smyth, S. S. (2015). Lysophospholipids in coronary artery and chronic ischemic heart disease. Current Opinion in Lipidology. doi:10.1097/MOL.0000000000000226.
Tan, M., Hao, F., Xu, X., Chisolm, G. M., & Cui, M. Z. (2009). Lysophosphatidylcholine activates a novel PKD2-mediated signaling pathway that controls monocyte migration. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Arteriosclerosis, Thrombosis, and Vascular Biology, 29(9), 1376–1382. doi:10.1161/ATVBAHA.109.191585.
Kurano, M., Suzuki, A., Inoue, A., Tokuhara, Y., Kano, K., Matsumoto, H., et al. (2015). Possible involvement of minor lysophospholipids in the increase in plasma lysophosphatidic acid in acute coronary syndrome. [Research Support, Non-U.S. Gov’t]. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(2), 463–470. doi:10.1161/ATVBAHA.114.304748.
McInnes, I. B., & Schett, G. (2011). The pathogenesis of rheumatoid arthritis. [Review]. New England Journal of Medicine, 365(23), 2205–2219. doi:10.1056/NEJMra1004965. 10.7748/phc2011.11.21.9.29.c8797.
Bourgoin, S. G., & Zhao, C. (2010). Autotaxin and lysophospholipids in rheumatoid arthritis. [Research Support, Non-U.S. Gov’t Review]. Current Opinion in Investigational Drugs, 11(5), 515–526.
Frasch, S. C., & Bratton, D. L. (2012). Emerging roles for lysophosphatidylserine in resolution of inflammation. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Progress in Lipid Research, 51(3), 199–207. doi:10.1016/j.plipres.2012.03.001.
Hung, N. D., Kim, M. R., & Sok, D. E. (2011). 2-Polyunsaturated acyl lysophosphatidylethanolamine attenuates inflammatory response in zymosan A-induced peritonitis in mice. [Research Support, Non-U.S. Gov’t]. Lipids, 46(10), 893–906. doi:10.1007/s11745-011-3589-2.
Marion-Letellier, R., Savoye, G., & Ghosh, S. (2015). Polyunsaturated fatty acids and inflammation. [Review]. IUBMB Life, 67(9), 659–667. doi:10.1002/iub.1428.
Basil, M. C., & Levy, B. D. (2016). Specialized pro-resolving mediators: endogenous regulators of infection and inflammation. Nature Reviews Immunology, 16(1), 51–67. doi:10.1038/nri.2015.4.
Chen, N. C., Yang, F., Capecci, L. M., Gu, Z., Schafer, A. I., Durante, W., et al. (2010). Regulation of homocysteine metabolism and methylation in human and mouse tissues. [Research Support, N.I.H., Extramural]. FASEB Journal, 24(8), 2804–2817. doi:10.1096/fj.09-143651.
Anliker, B., & Chun, J. (2004). Lysophospholipid G protein-coupled receptors. [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. Review]. Journal of Biological Chemistry, 279(20), 20555–20558. doi:10.1074/jbc.R400013200.
Davenport, A. P., Alexander, S. P., Sharman, J. L., Pawson, A. J., Benson, H. E., Monaghan, A. E., et al. (2013). International Union of Basic and Clinical Pharmacology. LXXXVIII. G protein-coupled receptor list: recommendations for new pairings with cognate ligands. [Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov’t Review]. Pharmacological Reviews, 65(3), 967–986. doi:10.1124/pr.112.007179.
Foord, S. M., Bonner, T. I., Neubig, R. R., Rosser, E. M., Pin, J. P., Davenport, A. P., et al. (2005). International Union of Pharmacology. XLVI. G protein-coupled receptor list. [Review]. Pharmacological Reviews, 57(2), 279–288. doi:10.1124/pr.57.2.5.
Chun, J., Goetzl, E. J., Hla, T., Igarashi, Y., Lynch, K. R., Moolenaar, W., et al. (2002). International Union of Pharmacology. XXXIV. Lysophospholipid receptor nomenclature. [Review]. Pharmacological Reviews, 54(2), 265–269.
Schmitz, G., & Ruebsaamen, K. (2010). Metabolism and atherogenic disease association of lysophosphatidylcholine. [Research Support, Non-U.S. Gov’t Review]. Atherosclerosis, 208(1), 10–18. doi:10.1016/j.atherosclerosis.2009.05.029.
Chun, J., Hla, T., Lynch, K. R., Spiegel, S., & Moolenaar, W. H. (2010). International Union of Basic and Clinical Pharmacology. LXXVIII. Lysophospholipid receptor nomenclature. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Pharmacological Reviews, 62(4), 579–587. doi:10.1124/pr.110.003111.
Guy, A. T., Nagatsuka, Y., Ooashi, N., Inoue, M., Nakata, A., Greimel, P., et al. (2015). NEURONAL DEVELOPMENT. Glycerophospholipid regulation of modality-specific sensory axon guidance in the spinal cord. [Research Support, Non-U.S. Gov’t]. Science, 349(6251), 974–977. doi:10.1126/science.aab3516.
Ikubo, M., Inoue, A., Nakamura, S., Jung, S., Sayama, M., Otani, Y., et al. (2015). Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174. [Research Support, Non-U.S. Gov’t]. Journal of Medicinal Chemistry, 58(10), 4204–4219. doi:10.1021/jm5020082.
Makide, K., Uwamizu, A., Shinjo, Y., Ishiguro, J., Okutani, M., Inoue, A., et al. (2014). Novel lysophospholipid receptors: their structure and function. [Research Support, Non-U.S. Gov’t Review]. Journal of Lipid Research, 55(10), 1986–1995. doi:10.1194/jlr.R046920.
Torkhovskaya, T. I., Ipatova, O. M., Zakharova, T. S., Kochetova, M. M., & Khalilov, E. M. (2007). Lysophospholipid receptors in cell signaling. [Review]. Biochemistry (Mosc), 72(2), 125–131.
Xiang, S. Y., Dusaban, S. S., & Brown, J. H. (2013). Lysophospholipid receptor activation of RhoA and lipid signaling pathways. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Biochimica et Biophysica Acta, 1831(1), 213–222. doi:10.1016/j.bbalip.2012.09.004.
Jiang, S. Y., Wei, C. C., Shang, T. T., Lian, Q., Wu, C. X., & Deng, J. Y. (2012). High glucose induces inflammatory cytokine through protein kinase C-induced toll-like receptor 2 pathway in gingival fibroblasts. [Research Support, Non-U.S. Gov’t]. Biochemical and Biophysical Research Communications, 427(3), 666–670. doi:10.1016/j.bbrc.2012.09.118.
Kim, H., Zamel, R., Bai, X. H., & Liu, M. (2013). PKC activation induces inflammatory response and cell death in human bronchial epithelial cells. [Research Support, Non-U.S. Gov’t]. PLoS ONE, 8(5), e64182. doi:10.1371/journal.pone.0064182.
Cataisson, C., Joseloff, E., Murillas, R., Wang, A., Atwell, C., Torgerson, S., et al. (2003). Activation of cutaneous protein kinase C alpha induces keratinocyte apoptosis and intraepidermal inflammation by independent signaling pathways. Journal of Immunology, 171(5), 2703–2713.
Kaminska, B. (2005). MAPK signalling pathways as molecular targets for anti-inflammatory therapy—from molecular mechanisms to therapeutic benefits. [Research Support, Non-U.S. Gov’t Review]. Biochimica et Biophysica Acta, 1754(1–2), 253–262. doi:10.1016/j.bbapap.2005.08.017.
Kyriakis, J. M., & Avruch, J. (2012). Mammalian MAPK signal transduction pathways activated by stress and inflammation: a 10-year update. [Review]. Physiological Reviews, 92(2), 689–737. doi:10.1152/physrev.00028.2011.
Ma, Z., Zhang, J., Du, R., Ji, E., & Chu, L. (2011). Rho kinase inhibition by fasudil has anti-inflammatory effects in hypercholesterolemic rats. [Research Support, Non-U.S. Gov’t]. Biological and Pharmaceutical Bulletin, 34(11), 1684–1689.
Taylor, A., Tang, W., Bruscia, E. M., Zhang, P. X., Lin, A., Gaines, P., et al. (2014). SRF is required for neutrophil migration in response to inflammation. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Blood, 123(19), 3027–3036. doi:10.1182/blood-2013-06-507582.
Watson, L., Tullus, K., Marks, S. D., Holt, R. C., Pilkington, C., & Beresford, M. W. (2012). Increased serum concentration of sphingosine-1-phosphate in juvenile-onset systemic lupus erythematosus. [Research Support, Non-U.S. Gov’t]. Journal of Clinical Immunology, 32(5), 1019–1025. doi:10.1007/s10875-012-9710-3.
Abu El-Asrar, A. M., Nawaz, M. I., Mohammad, G., Siddiquei, M. M., Alam, K., Mousa, A., et al. (2014). Expression of bioactive lysophospholipids and processing enzymes in the vitreous from patients with proliferative diabetic retinopathy. [Research Support, Non-U.S. Gov’t]. Lipids in Health and Disease, 13, 187. doi:10.1186/1476-511X-13-187.
Moreno-Navarrete, J. M., Catalan, V., Whyte, L., Diaz-Arteaga, A., Vazquez-Martinez, R., Rotellar, F., et al. (2012). The L-alpha-lysophosphatidylinositol/GPR55 system and its potential role in human obesity. [Research Support, Non-U.S. Gov’t]. Diabetes, 61(2), 281–291. doi:10.2337/db11-0649.
Zhao, C., Fernandes, M. J., Prestwich, G. D., Turgeon, M., Di Battista, J., Clair, T., et al. (2008). Regulation of lysophosphatidic acid receptor expression and function in human synoviocytes: implications for rheumatoid arthritis? [Comparative Study Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov’t]. Molecular Pharmacology, 73(2), 587–600. doi:10.1124/mol.107.038216.
Bektas, M., Allende, M. L., Lee, B. G., Chen, W., Amar, M. J., Remaley, A. T., et al. (2010). Sphingosine 1-phosphate lyase deficiency disrupts lipid homeostasis in liver. [Research Support, N.I.H., Extramural Research Support, N.I.H., intramural]. Journal of Biological Chemistry, 285(14), 10880–10889. doi:10.1074/jbc.M109.081489.
Takeshita, H., Kitano, M., Iwasaki, T., Kitano, S., Tsunemi, S., Sato, C., et al. (2012). Sphingosine 1-phosphate (S1P)/S1P receptor 1 signaling regulates receptor activator of NF-kappaB ligand (RANKL) expression in rheumatoid arthritis. [Research Support, Non-U.S. Gov’t]. Biochemical and Biophysical Research Communications, 419(2), 154–159. doi:10.1016/j.bbrc.2012.01.103.
Vladykovskaya, E., Ozhegov, E., Hoetker, J. D., Xie, Z., Ahmed, Y., Suttles, J., et al. (2011). Reductive metabolism increases the proinflammatory activity of aldehyde phospholipids. [Research Support, N.I.H., Extramural]. Journal of Lipid Research, 52(12), 2209–2225. doi:10.1194/jlr.M013854.
Anavi-Goffer, S., Baillie, G., Irving, A. J., Gertsch, J., Greig, I. R., Pertwee, R. G., et al. (2012). Modulation of L-alpha-lysophosphatidylinositol/GPR55 mitogen-activated protein kinase (MAPK) signaling by cannabinoids. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Journal of Biological Chemistry, 287(1), 91–104. doi:10.1074/jbc.M111.296020.
Henstridge, C. M., Balenga, N. A., Ford, L. A., Ross, R. A., Waldhoer, M., & Irving, A. J. (2009). The GPR55 ligand L-alpha-lysophosphatidylinositol promotes RhoA-dependent Ca2+ signaling and NFAT activation. [Research Support, Non-U.S. Gov’t]. FASEB Journal, 23(1), 183–193. doi:10.1096/fj.08-108670.
Imokawa, G., Takagi, Y., Higuchi, K., Kondo, H., & Yada, Y. (1999). Sphingosylphosphorylcholine is a potent inducer of intercellular adhesion molecule-1 expression in human keratinocytes. Journal of Investigative Dermatology, 112, 91–96.
Nishikawa, M., Kurano, M., Ikeda, H., Aoki, J., & Yatomi, Y. (2015). Lysophosphatidylserine has bilateral effects on macrophages in the pathogenesis of atherosclerosis. Journal of Atherosclerosis and Thrombosis, 22, 518–526.
Yin, Y., Li, X., Sha, X., Xi, H., Li, Y. F., Shao, Y., et al. (2015). Early hyperlipidemia promotes endothelial activation via a caspase-1-sirtuin 1 pathway. [Research Support, N.I.H., Extramural]. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(4), 804–816. doi:10.1161/ATVBAHA.115.305282.
Yudkin, J. S., Kumari, M., Humphries, S. E., & Mohamed-Ali, V. (2000). Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. Review]. Atherosclerosis, 148(2), 209–214.
Baker, R. G., Hayden, M. S., & Ghosh, S. (2011). NF-kappaB, inflammation, and metabolic disease. [Research Support, N.I.H., Extramural Review]. Cell Metabolism, 13(1), 11–22. doi:10.1016/j.cmet.2010.12.008.
Chen, G. Y., & Nunez, G. (2010). Sterile inflammation: sensing and reacting to damage. [Research Support, N.I.H., Extramural Review]. Nature Reviews Immunology, 10(12), 826–837. doi:10.1038/nri2873.
Kawai, T., & Akira, S. (2010). The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Review]. Nature Immunology, 11(5), 373–384. doi:10.1038/ni.1863.
Xi, H., Zhang, Y., Xu, Y., Yang, W. Y., Jiang, X., Sha, X., et al. (2016). Caspase-1 inflammasome activation mediates homocysteine-induced pyrop-apoptosis in endothelial cells. Circulation Research. doi:10.1161/CIRCRESAHA.116.308501.
Lopez-Pastrana, J., Ferrer, L. M., Li, Y. F., Xiong, X., Xi, H., Cueto, R., et al. (2015). Inhibition of caspase-1 activation in endothelial cells improves angiogenesis: A NOVEL THERAPEUTIC POTENTIAL FOR ISCHEMIA. [Research Support, N.I.H., Extramural]. Journal of Biological Chemistry, 290(28), 17485–17494. doi:10.1074/jbc.M115.641191.
Li, X., Fang, P., Li, Y., Kuo, Y.-M., Andrews, A. J., Nanayakkara, G., et al. (2016). Mitochondrial reactive oxygen species mediate lysophosphatidylcholine-induced endothelial cell activation. Atherosclerosis, Thrombosis and Vascular Biology. Article in press.
Oda, S. K., Strauch, P., Fujiwara, Y., Al-Shami, A., Oravecz, T., Tigyi, G., et al. (2013). Lysophosphatidic acid inhibits CD8 T cell activation and control of tumor progression. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Cancer Immunology Research, 1(4), 245–255. doi:10.1158/2326-6066.CIR-13-0043-T.
Hu, J., Oda, S. K., Shotts, K., Donovan, E. E., Strauch, P., Pujanauski, L. M., et al. (2014). Lysophosphatidic acid receptor 5 inhibits B cell antigen receptor signaling and antibody response. [Research Support, N.I.H., Extramural]. Journal of Immunology, 193(1), 85–95. doi:10.4049/jimmunol.1300429.
Emo, J., Meednu, N., Chapman, T. J., Rezaee, F., Balys, M., Randall, T., et al. (2012). Lpa2 is a negative regulator of both dendritic cell activation and murine models of allergic lung inflammation. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Journal of Immunology, 188(8), 3784–3790. doi:10.4049/jimmunol.1102956.
Saatian, B., Zhao, Y., He, D., Georas, S. N., Watkins, T., Spannhake, E. W., et al. (2006). Transcriptional regulation of lysophosphatidic acid-induced interleukin-8 expression and secretion by p38 MAPK and JNK in human bronchial epithelial cells. [Research Support, N.I.H., Extramural]. The Biochemical Journal, 393(Pt 3), 657–668. doi:10.1042/BJ20050791.
Sun, Q., Gao, W., Loughran, P., Shapiro, R., Fan, J., Billiar, T. R., et al. (2013). Caspase 1 activation is protective against hepatocyte cell death by up-regulating beclin 1 protein and mitochondrial autophagy in the setting of redox stress. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. Journal of Biological Chemistry, 288(22), 15947–15958. doi:10.1074/jbc.M112.426791.
Khan, D., & Ansar Ahmed, S. (2015). The immune system is a natural target for estrogen action: opposing effects of estrogen in two prototypical autoimmune diseases. [Review]. Frontiers in Immunology, 6, 635. doi:10.3389/fimmu.2015.00635.
Mai, J., Nanayakkara, G., Lopez-Pastrana, J., Li, X., Li, Y. F., Wang, X., et al. (2016). Interleukin-17A promotes aortic endothelial cell activation via transcriptionally and post-translationally activating p38 MAPK pathway. Journal of Biological Chemistry. doi:10.1074/jbc.M115.690081.
Taleb, S., Tedgui, A., & Mallat, Z. (2015). IL-17 and Th17 cells in atherosclerosis: subtle and contextual roles. [Research Support, Non-U.S. Gov’t Review]. Arteriosclerosis, Thrombosis, and Vascular Biology, 35(2), 258–264. doi:10.1161/ATVBAHA.114.303567.
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This work was partially supported by the National Institutes of Health Grants to XFY, HW, and JY, and the American Heart Association Postdoctoral Fellowship to Dr. YFL.
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N/A. This study only employed a data mining strategy and did not involve human participants or experimental animal models.
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Associate Editor Angela Taylor oversaw the review of this article
Ya-Feng Li, Gayani Nanayakkara, Ying Shao and Bin Liang contributed equally to this work.
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Wang, X., Li, YF., Nanayakkara, G. et al. Lysophospholipid Receptors, as Novel Conditional Danger Receptors and Homeostatic Receptors Modulate Inflammation—Novel Paradigm and Therapeutic Potential. J. of Cardiovasc. Trans. Res. 9, 343–359 (2016). https://doi.org/10.1007/s12265-016-9700-6
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DOI: https://doi.org/10.1007/s12265-016-9700-6