Ex vivo culture of mouse skin activates an interleukin 1 alpha-dependent inflammatory response.

Publisher: Munksgaard Country of Publication: Denmark NLM ID: 9301549 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1600-0625 (Electronic) Linking ISSN: 09066705 NLM ISO Abbreviation: Exp Dermatol Subsets: MEDLINE

Original Publication: Copenhagen : Munksgaard, c1992-

Inflammation/*genetics ; Interleukin-1alpha/*genetics ; Skin/*physiopathology; Animals ; Antibodies, Neutralizing/pharmacology ; Chemokine CXCL1/genetics ; Chemokine CXCL1/metabolism ; Inflammation/metabolism ; Inflammation/pathology ; Interleukin-1alpha/antagonists & inhibitors ; Interleukin-1alpha/metabolism ; Interleukin-1beta/antagonists & inhibitors ; Interleukin-1beta/genetics ; Interleukin-1beta/metabolism ; Interleukin-6/genetics ; Interleukin-6/metabolism ; Mice ; Mice, Knockout ; Myeloid Differentiation Factor 88/genetics ; Skin/pathology ; Tissue Culture Techniques

Ex vivo culture of mouse and human skin causes an inflammatory response characterized by production of multiple cytokines. We used ex vivo culture of mouse tail skin specimens to investigate mechanisms of this skin culture-induced inflammatory response. Multiplex assays revealed production of interleukin 1 alpha (IL-1α), interleukin 1 beta (IL-1β), interleukin 6 (IL-6), chemokine C-X-C motif ligand 1 (CXCL1), granulocyte colony-stimulating factor (G-CSF) and granulocyte-macrophage colony-stimulating factor (GM-CSF) during skin culture, and quantitative PCR revealed transcripts for these proteins were also increased. Ex vivo cultures of skin from myeloid differentiation primary response 88 deficient mice (Myd88 ^-/- ) demonstrated significantly reduced expression of transcripts for the aforementioned cytokines. The same result was observed with skin from interleukin 1 receptor type 1 deficient mice (Il1r1 ^-/- ). These data suggested the IL-1R1/MyD88 axis is required for the skin culture-induced inflammatory response and led us to investigate the role of IL-1α and IL-1β (the ligands for IL-1R1) in this process. Addition of IL-1α neutralizing antibody to skin cultures significantly reduced expression of Cxcl1, Il6 and Csf3. IL-1β neutralization did not reduce levels of these transcripts. These studies suggest that IL-1α promotes the skin the culture-induced inflammatory response.
(© 2019 This article is a U.S Government work and is in the public domain in the USA.)

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R01 AG048946 United States AG NIA NIH HHS; R01 ES020866 United States ES NIEHS NIH HHS; I01 CX001956 United States CX CSRD VA; T32 AR062495 United States AR NIAMS NIH HHS; R21 HL139934 United States HL NHLBI NIH HHS; IK2 CX001019 United States CX CSRD VA; R01 AI095282 United States AI NIAID NIH HHS; International Ralph W. and Grace M. Showalter Research Trust Fund

Keywords: IL-1α; cytokines; explant; keratinocytes; mice

0 (Antibodies, Neutralizing)
0 (Chemokine CXCL1)
0 (Cxcl1 protein, mouse)
0 (IL1B protein, mouse)
0 (Il1a protein, mouse)
0 (Interleukin-1alpha)
0 (Interleukin-1beta)
0 (Interleukin-6)
0 (Myd88 protein, mouse)
0 (Myeloid Differentiation Factor 88)
0 (interleukin-6, mouse)

Date Created: 20191001 Date Completed: 20210601 Latest Revision: 20250128

20250128

PMC7184933

10.1111/exd.14044

31566815