The Effect of Capsaicin on Neuroinflammatory Mediators of Rosacea

Overview

Journal Ann Dermatol

Specialty Dermatology

Date 2022 Aug 10

PMID 35948328

Authors

Hyeon Bin Kim

Eui Young Na

Sook Jung Yun

Jee-Bum Lee

Affiliations

Soon will be listed here.

Abstract

Background: Rosacea is a chronic inflammatory skin disease with a pathophysiological mechanism that remains unclear. Recently, dysregulation of the sensory nerve system has been implicated in the development of this condition.

Objective: This study aimed to investigate the effect of capsaicin on neuroinflammatory mediators in rosacea. In addition, this study aimed to evaluate the attenuating effects of capsazepine, a transient receptor potential vanilloid type 1 (TRPV1) antagonist.

Methods: We obtained skin tissue from both rosacea patients and normal individuals for an study. In addition, normal human epidermal keratinocytes (NHEKs) were cultured, and treated with capsaicin and capsazepine for an study. Quantitative changes in neuroinflammatory mediators were evaluated by semi-quantitative reverse transcription-polymerase chain reaction (PCR), real-time PCR, enzyme-linked immunosorbent assay, and immunofluorescence staining.

Results: The data showed the increase of TRPV1, TRPV4, cathelicidin (LL37) and tumor necrosis factor-α (TNF-α) in skin tissue by real-time PCR. In addition, the data showed that cathelicidin (LL37), kallikrein-5 (KLK-5), TNF-α, vascular endothelial growth factor (VEGF), interleukin (IL)-1α, IL-1β, IL-8, and protease-activated receptor 2 (PAR2) increased in capsaicin-treated NHEKs. Capsazepine attenuated the expression of TRPV1 and other mediators, except for IL-8, in capsaicin-treated NHEKs.

Conclusion: We confirmed that TRPV1, TRPV4, cathelicidin (LL37) and TNF-α are increased in rosacea skin, and that capsaicin is associated with increase of neuroinflammatory mediators such as LL37, KLK-5, TNF-α, VEGF, IL-1α, IL-1β, IL-8, and PAR2. Modulators or inhibitors of neuroinflammatory mediators including TRPV1 could be potential therapeutic option in the treatment of patients with rosacea.

Citing Articles

Update on protease-activated receptor 2 in inflammatory and autoimmune dermatological diseases.

Xu K, Wang L, Lin M, He G Front Immunol. 2024; 15:1449126.

PMID: 39364397 PMC: 11446762. DOI: 10.3389/fimmu.2024.1449126.

Signaling pathways and targeted therapy for rosacea.

Yang F, Wang L, Song D, Zhang L, Wang X, Du D Front Immunol. 2024; 15:1367994.

PMID: 39351216 PMC: 11439730. DOI: 10.3389/fimmu.2024.1367994.

The role of TRPV1 in RA pathogenesis: worthy of attention.

Qu Y, Fu Y, Liu Y, Liu C, Xu B, Zhang Q Front Immunol. 2023; 14:1232013.

PMID: 37744324 PMC: 10514908. DOI: 10.3389/fimmu.2023.1232013.

New Insights into the Mutual Promotion of Rosacea, Anxiety, and Depression from Neuroendocrine Immune Aspects.

Yang X, Cai M Clin Cosmet Investig Dermatol. 2023; 16:1363-1371.

PMID: 37275216 PMC: 10238710. DOI: 10.2147/CCID.S413237.

References

Roosterman D, Goerge T, Schneider S, Bunnett N, Steinhoff M . Neuronal control of skin function: the skin as a neuroimmunoendocrine organ. Physiol Rev. 2006; 86(4):1309-79. DOI: 10.1152/physrev.00026.2005. View

Gerber P, Buhren B, Steinhoff M, Homey B . Rosacea: The cytokine and chemokine network. J Investig Dermatol Symp Proc. 2011; 15(1):40-7. PMC: 3704141. DOI: 10.1038/jidsymp.2011.9. View

Two A, Del Rosso J . Kallikrein 5-mediated inflammation in rosacea: clinically relevant correlations with acute and chronic manifestations in rosacea and how individual treatments may provide therapeutic benefit. J Clin Aesthet Dermatol. 2014; 7(1):20-5. PMC: 3930536. View

Frias B, Merighi A . Capsaicin, Nociception and Pain. Molecules. 2016; 21(6). PMC: 6273518. DOI: 10.3390/molecules21060797. View

Sanchez J, Berlingeri-Ramos A, Dueno D . Granulomatous rosacea. Am J Dermatopathol. 2008; 30(1):6-9. DOI: 10.1097/DAD.0b013e31815bc191. View

Buddenkotte J, Steinhoff M . Recent advances in understanding and managing rosacea. F1000Res. 2019; 7. PMC: 6281021. DOI: 10.12688/f1000research.16537.1. View

Steinhoff M, Buddenkotte J, Aubert J, Sulk M, Novak P, Schwab V . Clinical, cellular, and molecular aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011; 15(1):2-11. PMC: 3704130. DOI: 10.1038/jidsymp.2011.7. View

Scharschmidt T, Yost J, Truong S, Steinhoff M, Wang K, Berger T . Neurogenic rosacea: a distinct clinical subtype requiring a modified approach to treatment. Arch Dermatol. 2011; 147(1):123-6. PMC: 3692271. DOI: 10.1001/archdermatol.2010.413. View

Yamasaki K, Gallo R . The molecular pathology of rosacea. J Dermatol Sci. 2009; 55(2):77-81. PMC: 2745268. DOI: 10.1016/j.jdermsci.2009.04.007. View

10.

Steinhoff M, Schauber J, Leyden J . New insights into rosacea pathophysiology: a review of recent findings. J Am Acad Dermatol. 2013; 69(6 Suppl 1):S15-26. DOI: 10.1016/j.jaad.2013.04.045. View

11.

Jeon H, Na E, Yun S, Lee S, Lee J . Citron Essential Oils Alleviate the Mediators Related to Rosacea Pathophysiology in Epidermal Keratinocytes. Ann Dermatol. 2021; 30(6):653-661. PMC: 7992447. DOI: 10.5021/ad.2018.30.6.653. View

12.

Ahn C, Huang W . Rosacea Pathogenesis. Dermatol Clin. 2018; 36(2):81-86. DOI: 10.1016/j.det.2017.11.001. View

13.

Braga Ferreira L, Faria J, Dos Santos J, Xavier Faria R . Capsaicin: TRPV1-independent mechanisms and novel therapeutic possibilities. Eur J Pharmacol. 2020; 887:173356. DOI: 10.1016/j.ejphar.2020.173356. View

14.

Gomaa A, Yaar M, Eyada M, Bhawan J . Lymphangiogenesis and angiogenesis in non-phymatous rosacea. J Cutan Pathol. 2007; 34(10):748-53. DOI: 10.1111/j.1600-0560.2006.00695.x. View

15.

Huggenberger R, Detmar M . The cutaneous vascular system in chronic skin inflammation. J Investig Dermatol Symp Proc. 2011; 15(1):24-32. PMC: 3398151. DOI: 10.1038/jidsymp.2011.5. View

16.

Cribier B . Rosacea under the microscope: characteristic histological findings. J Eur Acad Dermatol Venereol. 2013; 27(11):1336-43. DOI: 10.1111/jdv.12121. View

17.

Sulk M, Seeliger S, Aubert J, Schwab V, Cevikbas F, Rivier M . Distribution and expression of non-neuronal transient receptor potential (TRPV) ion channels in rosacea. J Invest Dermatol. 2011; 132(4):1253-62. PMC: 3305847. DOI: 10.1038/jid.2011.424. View

18.

Schwab V, Sulk M, Seeliger S, Nowak P, Aubert J, Mess C . Neurovascular and neuroimmune aspects in the pathophysiology of rosacea. J Investig Dermatol Symp Proc. 2011; 15(1):53-62. PMC: 3704331. DOI: 10.1038/jidsymp.2011.6. View

19.

Gibbons C, Wang N, Freeman R . Capsaicin induces degeneration of cutaneous autonomic nerve fibers. Ann Neurol. 2010; 68(6):888-98. PMC: 3057686. DOI: 10.1002/ana.22126. View

20.

van Zuuren E . Rosacea. N Engl J Med. 2017; 377(18):1754-1764. DOI: 10.1056/NEJMcp1506630. View