Decreased expression of G-protein-coupled receptors GPR43 and GPR109a in psoriatic skin can be restored by topical application of sodium butyrate
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The G-protein-coupled receptors GPR43 and GPR109a are known to play an important role in mediating anti-inflammatory and anti-cancer functions in the gut. Short-chain fatty acids, such as sodium butyrate (SB), are activators of GPR43 and GPR109a and thereby promote anti-inflammatory effects. The present study aimed to examine the expression of these receptors and their reaction to SB in psoriasis. Lesional and non-lesional biopsies of 6 psoriasis patients and of 4 controls were obtained and stained for GPR109a and GPR43. Ex vivo stimulation with SB was performed on fresh biopsy material. Lesional and non-lesional psoriatic skin showed a decreased expression of GPR109a and GPR43 on keratinocytes in comparison with control skin. Topical application of SB was able to increase the low-level expression of both receptors. The data suggest that SB by restoring the impaired expression of GPR109a and GPR43 might exert anti-inflammatory effects and may be utilized as a topical tool for the treatment of psoriasis, which has to be proven in future clinical trials.
KeywordsPsoriasis G-protein-coupled receptor Sodium butyrate Inflammation Treatment
Short-chain fatty acids
Regulatory T cell(s)
We thank Ms. Katharina Pallasch for excellent technical assistance.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed consent was obtained from all individual participants included in the study.
- 12.Ghoreschi K, Thomas P, Breit S, Dugas M, Mailhammer R, van Eden W, van der Zee R, Biedermann T, Prinz J, Mack M, Mrowietz U, Christophers E, Schlöndorff D, Plewig G, Sander CA, Röcken M (2003) Interleukin-4 therapy of psoriasis induces Th2 responses and improves human autoimmune disease. Nat Med 9:40–46CrossRefPubMedGoogle Scholar
- 13.Iraporda C, Errea A, Romanin DE, Cayet D, Pereyra E, Pignataro O, Sirard JC, Garrote GL, Abraham AG, Rumbo M (2015) Lactate and short chain fatty acids produced by microbial fermentation downregulate proinflammatory responses in intestinal epithelial cells and myeloid cells. Immunobiology 220:1161–1169CrossRefPubMedGoogle Scholar
- 14.Jeninga EH, Bugge A, Nielsen R, Kersten S, Hamers N, Dani C, Wabitsch M, Berger R, Stunnenberg HG, Mandrup S, Kalkhoven E (2009) Peroxisome proliferator-activated receptor gamma regulates expression of the anti-lipolytic G-protein-coupled receptor 81 (GPR81/Gpr81). J Biol Chem 284:26385–26393CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Singh N, Gurav A, Sivaprakasam S, Brady E, Padia R, Shi H, Thangaraju M, Prasad PD, Manicassamy S, Munn DH, Lee JR, Offermanns S, Ganapathy V (2014) Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis. Immunity 40:128–139CrossRefPubMedPubMedCentralGoogle Scholar