T helper 1 and 2 stimuli induce distinct phenotypes in gingival fibroblasts.

Abstract:

OBJECTIVE:Gingival fibroblasts (GFs) can participate in the immune response and play an immune-regulatory role. This study was to evaluate whether GFs can be differently activated and polarized into distinct functional subtypes in response to T helper type 1 (Th1), or Th2 stimuli. DESIGN:Human GFs were stimulated by the Th1 cytokine, IFN-γ, and lipopolysaccharide (LPS), separately or in combination (Th1 stimuli), or by Th2 cytokines, IL-4 and IL-13, separately or in combination (Th2 stimuli). mRNA expression of pro-inflammatory cytokines (IL-1β, IL-6, IL-12), anti-inflammatory cytokines (IL-4, IL-10, IL-13), chemokines ((C-X-C motif chemokine (CXCL)10, CXCL11, C-C motif ligand 20), molecules involved in antigen presentation ((human leukocyte antigen (HLA)-ABC, HLA-DP, CD74, CD40)), LPS-recognizing components (Toll-like receptor 4, CD14), collagen type 1 (COL1), matrix metalloproteinase (MMP)-1, and inducible nitric oxide synthase (iNOS) and the protein levels of IL-6, CXCL11, CD14, and COL1 accumulated in supernatants were analyzed using real-time PCR and ELISA, respectively. The cell surface levels of the molecules involved in antigen presentation were detected by flow cytometry. RESULTS:Th1 stimuli strongly upregulated the expression of diverse cytokines, chemokines, molecules involved in antigen presentation, LPS-recognizing components, MMP-1, and iNOS, whereas Th1 stimuli inhibited the expression of COLI. In contrast, Th2 stimuli strongly upregulated the levels of COL1 and IL-4, while the expression levels of the other factors were minimally affected or even inhibited. CONCLUSION:These results show that GFs can be polarized into functionally distinct subtypes, immune-activating but tissue-destructive GF1 or tissue-reparative GF2, in response to Th1 and Th2 stimuli, respectively.

journal_name

Arch Oral Biol

journal_title

Archives of oral biology

authors

Jang JY,Baek KJ,Choi Y,Ji S

doi

10.1016/j.archoralbio.2019.04.019

subject

Has Abstract

pub_date

2019-06-01 00:00:00

pages

171-178

eissn

0003-9969

issn

1879-1506

pii

S0003-9969(19)30051-2

journal_volume

102

pub_type

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