Activation of NLRP3 Inflammasome by Palmitic Acid in Human Sebocytes
1
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Sebocytes are the main cells involved in the pathogenesis of acne by producing lipids and inflammatory cytokines. Although palmitic acid (PA) has been suggested to induce an inflammatory reaction, its effect on sebocytes remains to be elucidated. Objective: In the present study, we investigated whether PA promotes inflammasome-mediat- ed inflammation of sebocytes both and . Methods: We intradermally injected PA into the mice ears. And, we treated cultured human sebocytes with PA. Inflammasome-mediated inflammation was verified by immunohisto- chemistry, Western blot and ELISA. Results: PA-treated mice developed an inflammatory response associated with increased in- terleukin (IL)-1β expression in the sebaceous glands. When PA was added to cultured human sebocytes, caspase-1 activation and IL-1β secretion were significantly enhanced. In addition, NLRP3 knockdown attenuated IL-1β production by sebocytes stimulated with PA. PA-medi- ated inflammasome activation required reactive oxygen species. Conclusion: These findings indicate that PA activates the NLRP3 inflammasome before in- duction of an inflammatory response in sebocytes. Thus, PA may play a role in the inflamma- tion of acne.
Abstract
Background: Sebocytes are the main cells involved in the pathogenesis of acne by producing lipids and inflammatory cytokines. Although palmitic acid (PA) has been suggested to induce an inflammatory reaction, its effect on sebocytes remains to be elucidated. Objective: In the present study, we investigated whether PA promotes inflammasome-mediat- ed inflammation of sebocytes both and . Methods: We intradermally injected PA into the mice ears. And, we treated cultured human sebocytes with PA. Inflammasome-mediated inflammation was verified by immunohisto- chemistry, Western blot and ELISA. Results: PA-treated mice developed an inflammatory response associated with increased in- terleukin (IL)-1β expression in the sebaceous glands. When PA was added to cultured human sebocytes, caspase-1 activation and IL-1β secretion were significantly enhanced. In addition, NLRP3 knockdown attenuated IL-1β production by sebocytes stimulated with PA. PA-medi- ated inflammasome activation required reactive oxygen species. Conclusion: These findings indicate that PA activates the NLRP3 inflammasome before in- duction of an inflammatory response in sebocytes. Thus, PA may play a role in the inflamma- tion of acne.
참고문헌 (28)
- 정인순, "The Difference in Sebum Secretion Affecting Development of Acne", Annals of Dermatology, 31(4), pp.426~433 (2019), 대한피부과학회[DOI]
- Qin M, "Propionibacterium acnes Induces IL-1β secretion via the NLRP3 inflammasome in human monocytes", J Invest Dermatol, 134, pp.381~388 (2014)
- Kistowska M, "IL-1β drives inflammatory responses to propionibacterium acnes in vitro and in vivo", J Invest Dermatol, 134, pp.677~685 (2014)
- Li ZJ, "Propionibacterium acnes activates the NLRP3 inflammasome in human sebocytes", J Invest Dermatol, 134, pp.2747~2756 (2014)
- Wen H, "Fatty acid-induced NLRP3-ASC inflammasome activation interferes with insulin signaling", Nat Immunol, 12, pp.408~415 (2011)
- Yan Y, "Omega-3 fatty acids prevent inflammation and metabolic disorder through inhibition of NLRP3 inflammasome activation", Immunity, 38, pp.1154~1163 (2013)
- Snodgrass RG, "Inflammasome-mediated secretion of IL-1β in human monocytes through TLR2 activation; modulation by dietary fatty acids", J Immunol, 191, pp.4337~4347 (2013)
- Korbecki J, "The effect of palmitic acid on inflammatory response in macrophages : an overview of molecular mechanisms", Inflamm Res, 68, pp.915~932 (2019)
- Zouboulis CC, "Acne is an inflammatory disease and alterations of sebum composition initiate acne lesions", J Eur Acad Dermatol Venereol, 28, pp.527~532 (2014)
- Moradi Tuchayi S, "Acne vulgaris", Nat Rev Dis Primers, 1, pp.15029~ (2015)
- Ottaviani M, "Lipid mediators in acne", Mediators Inflamm, 2010, pp.858176~ (2010)
- Lwin SM, "Acne, quorum sensing and danger", Clin Exp Dermatol, 39, pp.162~167 (2014)
- Zhou BR, "Palmitic acid induces production of proinflammatory cytokines interleukin-6, interleukin-1β, and tumor necrosis factor-α via a NF-κBdependent mechanism in HaCaT keratinocytes", Mediators Inflamm, 2013, pp.530429~ (2013)
- Hwang YL, "Inhibitory effect of imperatorin on insulin-like growth factor-1-induced sebum production in human sebocytes cultured in vitro", Life Sci, 144, pp.49~53 (2016)
- Schroder K, "The NLRP3 inflammasome : a sensor for metabolic danger", Science, 327, pp.296~300 (2010)
- Martinon F, "The inflammasome : a molecular platform triggering activation of inflammatory caspases and processing of proIL-beta", Mol Cell, 10, pp.417~426 (2002)
- Nambayan RJT, "The inflammasome adapter ASC assembles into filaments with integral participation of its two Death Domains, PYD and CARD", J Biol Chem, 294, pp.439~452 (2019)
- Katsuta Y, "Unsaturated fatty acids induce calcium influx into keratinocytes and cause abnormal differentiation of epidermis", J Invest Dermatol, 124, pp.1008~1013 (2005)
- Akamatsu H, "Effect of palmitic acid on neutrophil functions in vitro", Int J Dermatol, 40, pp.640~643 (2001)
- Kim J, "Activation of toll-like receptor 2 in acne triggers inflammatory cytokine responses", J Immunol, 169, pp.1535~1541 (2002)
- Mills OH, "Addressing free radical oxidation in acne vulgaris", J Clin Aesthet Dermatol, 9, pp.25~30 (2016)
- Ottaviani M, "Peroxidated squalene induces the production of inflammatory mediators in HaCaT keratinocytes : a possible role in acne vulgaris", J Invest Dermatol, 126, pp.2430~2437 (2006)
- Melnik B, "Dietary intervention in acne : attenuation of increased mTORC1 signaling promoted by Western diet", Dermatoendocrinol, 4, pp.20~32 (2012)
- Jung JY, "The influence of dietary patterns on acne vulgaris in Koreans", Eur J Dermatol, 20, pp.768~772 (2010)
- Ulvestad M, "Acne and dairy products in adolescence : results from a Norwegian longitudinal study", J Eur Acad Dermatol Venereol, 31, pp.530~535 (2017)
- Marty-Roix R, "(De-)oiling inflammasomes", Immunity, 38, pp.1088~1090 (2013)
- Khayef G, "Effects of fish oil supplementation on inflammatory acne", Lipids Health Dis, 11, pp.165~ (2012)
- Jung JY, "Effect of dietary supplementation with omega-3 fatty acid and gamma-linolenic acid on acne vulgaris: a randomised, double-blind, controlled trial", Acta Derm Venereol, 94, pp.521~525 (2014)