Hyaluronan Oligosaccharides Improve Rosacea-Like Phenotype through Anti-Inflammatory and Epidermal Barrier-Improving Effects
2
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
Background: Rosacea is a common skin disease associated with increased expression of cathelicidin, kallikrein 5 (KLK5), toll-like receptor (TLR) 2, and abnormal barrier function. Recently, it was reported that hyaluronan (HA) could influence immune function via various receptors and HA oligosaccharides (oligo-HAs) could suppress TLR-dependent cytokine expression. Objective: We investigated if oligo-HAs could influence on inflammation and epidermal barrier induced by LL-37, which had a major role in rosacea. Methods: We cultured normal human keratinocytes and treated them with LL-37 and oligo-HAs or the LL-37 alone. A rosacea-like BALB/c mouse model injected with LL-37 was used to determine the role of oligo-HAs in rosacea in vivo. Results: Interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α release was suppressed when keratinocytes were co-treated with oligo- HAs and LL-37 compared with keratinocytes treated with LL-37 only. Treatment with oligo-HAs resulted in decreased transepidermal water loss as well as improved redness. Decreased inflammatory cell infiltration, IL-17A and KLK5 expression and increased CD44 and filaggrin expression were also noted. Conclusion: Our findings suggest that oligo-HA improves rosacea-like phenotype through anti-inflammatory and epidermal barrier improving effect.
Abstract
Background: Rosacea is a common skin disease associated with increased expression of cathelicidin, kallikrein 5 (KLK5), toll-like receptor (TLR) 2, and abnormal barrier function. Recently, it was reported that hyaluronan (HA) could influence immune function via various receptors and HA oligosaccharides (oligo-HAs) could suppress TLR-dependent cytokine expression. Objective: We investigated if oligo-HAs could influence on inflammation and epidermal barrier induced by LL-37, which had a major role in rosacea. Methods: We cultured normal human keratinocytes and treated them with LL-37 and oligo-HAs or the LL-37 alone. A rosacea-like BALB/c mouse model injected with LL-37 was used to determine the role of oligo-HAs in rosacea in vivo. Results: Interleukin-8 (IL-8) and tumor necrosis factor (TNF)-α release was suppressed when keratinocytes were co-treated with oligo- HAs and LL-37 compared with keratinocytes treated with LL-37 only. Treatment with oligo-HAs resulted in decreased transepidermal water loss as well as improved redness. Decreased inflammatory cell infiltration, IL-17A and KLK5 expression and increased CD44 and filaggrin expression were also noted. Conclusion: Our findings suggest that oligo-HA improves rosacea-like phenotype through anti-inflammatory and epidermal barrier improving effect.
참고문헌 (26)
- Powell FC, "Clinical practice. Rosacea", N Engl J Med, 352, pp.793~803 (2005)
- Yamasaki K, "Increased serine protease activity and cathelicidin promotes skin inflammation in rosacea", Nat Med, 13, pp.975~980 (2007)
- Steinhoff M, "Clinical, cellular, and molecular aspects in the pathophysiology of rosacea", J Investig Dermatol Symp Proc, 15, pp.2~11 (2011)
- Steinhoff M, "New insights into rosacea pathophysiology : a review of recent findings", J Am Acad Dermatol, 69(6 Suppl 1), pp.S15~S26 (2013)
- Yamasaki K, "Rosacea as a disease of cathelicidins and skin innate immunity", J Investig Dermatol Symp Proc, 15, pp.12~15 (2011)
- Two AM, "Reduction in serine protease activity correlates with improved rosacea severity in a small, randomized pilot study of a topical serine protease inhibitor", J Invest Dermatol, 134, pp.1143~1145 (2014)
- Ní Raghallaigh S, "The fatty acid profile of the skin surface lipid layer in papulopustular rosacea", Br J Dermatol, 166, pp.279~287 (2012)
- Ní Raghallaigh S, "Epidermal hydration levels in patients with rosacea improve after minocycline therapy", Br J Dermatol, 171, pp.259~266 (2014)
- Stern R, "Hyaluronan in skin : aspects of aging and its pharmacologic modulation", Clin Dermatol, 26, pp.106~122 (2008)
- Bourguignon LY, "Selective matrix(hyaluronan)interaction with CD44 and RhoGTPase signaling promotes keratinocyte functions and overcomes age-related epidermal dysfunction", J Dermatol Sci, 72, pp.32~44 (2013)
- Black KE, "Hyaluronan fragments induce IFNβ via a novel TLR4-TRIF-TBK1-IRF3-dependent pathway", J Inflamm(Lond), 10, pp.23~ (2013)
- Kim MY, "Hyaluronic acid oligosaccharides suppress TLR3-dependent cytokine expression in a TLR4-dependent manner", PLoS One, 8, pp.e72421~ (2013)
- Slevin M, "Hyaluronan-mediated angiogenesis in vascular disease : uncovering RHAMM and CD44 receptor signaling pathways", Matrix Biol, 26, pp.58~68 (2007)
- Bourguignon LY, "Hyaluronan-CD44 interaction stimulates keratinocyte differentiation, lamellar body formation", secretion, and permeability barrier homeostasis, 2006, pp.126, 1356~1365
- Kage M, "Hyaluronan tetrasaccharides stimulate ceramide production through upregulated mRNA expression of ceramide synthesis-associated enzymes", Arch Dermatol Res, 308, pp.95~101 (2016)
- Dajnoki Z, "Sebaceous gland-rich skin is characterized by TSLP expression and distinct immune surveillance which is disturbed in rosacea", J Invest Dermatol, 137, pp.1114~1125 (2017)
- Gerber PA, "Rosacea : the cytokine and chemokine network", J Investig Dermatol Symp Proc, 15, pp.40~47 (2011)
- Senra L, "Keratinocyte-derived IL-17E contributes to inflammation in psoriasis", J Invest Dermatol, 136, pp.1970~1980 (2016)
- Richters R, "What is sensitive skin? A systematic literature review of objective measurements", Skin Pharmacol Physiol, 28, pp.75~83 (2015)
- Oe M, "Oral hyaluronan relieves wrinkles: a double-blinded, placebo-controlled study over a 12-week period", Clin Cosmet Investig Dermatol, 10, pp.267~273 (2017)
- Noble PW, "Matrix regulation of lung injury, inflammation, and repair: the role of innate immunity", Proc Am Thorac Soc, 3, pp.401~404 (2006)
- Liang J, "CD44is a negative regulator of acute pulmonary inflammation and lipopolysaccharide-TLR signaling in mouse macrophages", J Immunol, 178, pp.2469~2475 (2007)
- Teder P, "Resolution of lung inflammation by CD44", Science, 296, pp.155~158 (2002)
- Muto J, "Engagement of CD44 by hyaluronan suppresses TLR4 signaling and the septic response to LPS", Mol Immunol, 47, pp.449~456 (2009)
- Whitfeld M, "Staphylococcus epidermidis : a possible role in the pustules of rosacea", J Am Acad Dermatol, 64, pp.49~52 (2011)
- Kirschner N, "CD44 regulates tight-junction assembly and barrier function", J Invest Dermatol, 131, pp.932~943 (2011)