Tpl2 contributes to IL-1β-induced IL-8 expression via ERK1/2 activation in canine dermal fibroblasts.
Animals
Blotting, Western
Cells, Cultured
Dogs
Interleukin-1beta
/ pharmacology
Interleukin-8
/ metabolism
MAP Kinase Kinase Kinases
/ genetics
Male
Mitogen-Activated Protein Kinase 1
/ genetics
Mitogen-Activated Protein Kinase 3
/ genetics
RNA, Small Interfering
/ genetics
Real-Time Polymerase Chain Reaction
Journal
PloS one
ISSN: 1932-6203
Titre abrégé: PLoS One
Pays: United States
ID NLM: 101285081
Informations de publication
Date de publication:
2021
2021
Historique:
received:
11
08
2021
accepted:
21
10
2021
entrez:
4
11
2021
pubmed:
5
11
2021
medline:
7
1
2022
Statut:
epublish
Résumé
In autoimmune diseases, fibroblasts produce and secrete various cytokines and act as sentinel immune cells during inflammatory states. However, the contribution of sentinel immune cells (i.e. dermal fibroblasts) in autoimmune diseases of the skin, such as atopic dermatitis, has been obscure. The pro-inflammatory cytokine interleukin 1β (IL-1β) induces the expression of chemokines, such as interleukin 8 (IL-8), in autoimmune diseases of the skin. IL-8 induces the activation and recruitment of innate immune cells such as neutrophils to the site of inflammation. IL-1β-mediated induction of IL-8 expression is important for the pathogenesis of autoimmune diseases; however, the intracellular singling remains to be understood. To elucidate the mechanism of the onset of autoimmune diseases, we established a model for IL-1β-induced dermatitis and investigated MAPK signaling pathways in IL-1β-induced IL-8 expression. We also identified that a MAP3K Tpl2 acts as an upstream modulator of IL-1β-induced ERK1/2 activation in dermal fibroblasts. We observed an increase in the expression of IL-8 mRNA and protein in cells treated with IL-1β. ERK1/2 inhibitors significantly reduced IL-1β-induced IL-8 expression, whereas the inhibitor for p38 MAPK or JNK had no effect. IL-1β induced ERK1/2 phosphorylation, which was attenuated in the presence of an ERK1/2 inhibitor. IL-1β failed to induce IL-8 expression in cells transfected with siRNA for ERK1, or ERK2. Notably, a Tpl2 inhibitor reduced IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. We confirmed that the silencing of Tpl2 in siRNA-transfected fibroblasts prevented both in IL-1β-induced IL-8 expression and ERK1/2 phosphorylation. Taken together, our data indicate the importance of Tpl2 in the modulation of ERK1/2 signaling involved in the IL-1β-induced development of autoimmune diseases affecting the dermal tissue, such as atopic dermatitis.
Identifiants
pubmed: 34735542
doi: 10.1371/journal.pone.0259489
pii: PONE-D-21-25732
pmc: PMC8568182
doi:
Substances chimiques
Interleukin-1beta
0
Interleukin-8
0
RNA, Small Interfering
0
Mitogen-Activated Protein Kinase 1
EC 2.7.11.24
Mitogen-Activated Protein Kinase 3
EC 2.7.11.24
MAP Kinase Kinase Kinases
EC 2.7.11.25
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e0259489Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
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