CCL3, IL-7, IL-13 and IFN-γ were more expressed in skin's biopsy of patients with SSc (P = 0.0002, P = 0.0082, P = 0.0243, P = 0.0335, respectively) when compared with healthy controls.
Moreover, WKYMVm treatment reduced the serum levels of inflammatory cytokines, such as tumor necrosis factor-α, and interferon-γ, in the scleroderma model of wild-type mice but not in Fpr2 knockout mice.
We show that <i>GSDMA</i> is upregulated in SSc MDMs (P=8.4×10<sup>-4</sup>) but not in the skin, and is a significant eQTL in SSc macrophages and lipopolysaccharide/interferon gamma (IFNγ)-stimulated monocytes.
We observed in both PSS (IFN-γ: 174.9 pg/mL; TNF-α: 25.1 pg/mL) and FU (IFN-γ: 25.4 pg/mL; TNF-α: 27.2 pg/mL) groups a significantly increased level of T-helper 1 immune mediators compared to controls (IFN-γ, TNF-α: 0 pg/mL) [median].
We aimed to analyze IL-10+ Breg (B10) cells, found to be reduced in systemic sclerosis (SSc), in relation to SSc-specific autoAbs and IL-17+ and IFNγ+ T cells in SSc.
Genotype-mRNA expression correlation analysis revealed that the IRF8 protective allele was associated with increased interferon-gamma (IFN-γ) expression (P = 0.03) in patients with SSc but decreased type I IFN (IFIT1) expression in patients and controls (P = 0.02).
Importantly, the inhibition of type I collagen production induced by the Th17 clone supernatants was completely abrogated by blockade of IL-17A, TNF and IFN-γ mostly in SSc fibroblasts, revealing an intrinsic resistance to inhibitory signals in SSc.
SSc alveolar T lymphocytes expressed a cytokine profile suggestive of a mixed Th1/Th2 reaction, showing an increased frequency of mRNA for interleukin (IL)-10, IL-6 and interferon (IFN)γ, while IL-1β, IFNγ and tumour necrosis factor β were expressed in blood T lymphocytes in a higher percentage of patients with SSc than controls.
The MDR analysis showed a significant epistatic interaction among the interleukin-2 (IL-2) G-330T, IL-6 C-174G, and interferon-gamma AUTR5644T SNPs and the IL-1 receptor Cpst1970T, IL-6 Ant565G, and IL-10 C-819T SNPs in lcSSc and dcSSc susceptibility, respectively.
Using a reverse transcriptase-polymerase chain reaction technique, interleukin-4 (IL-4), IL-5, and interferon-gamma (IFNgamma) messenger RNA (mRNA) were measured in unseparated CD8+ and CD4+ bronchoalveolar lavage (BAL) cells from SSc patients and healthy controls.
The enhancement of collagenase gene expression by TNF-R55-specific TNF-alpha was augmented by simultaneous treatment of normal and scleroderma skin fibroblasts with interferon-gamma, indicating specific enhancement of TNF-R55 signaling pathway by interferon-gamma.
MAb against intercellular adhesion molecule type 1 (ICAM-1) and LFA-1 also prevented binding of T lymphocytes, but had a more marked effect on adhesion to SSc fibroblasts than to normal fibroblasts; they also completely abolished the increased binding to fibroblasts treated with interleukin-1 alpha, tumor necrosis factor alpha, and interferon-gamma.
In addition, interferon gamma (IFN-gamma) inhibits the constitutively increased collagen synthesis characteristic of fibroblasts derived from lesions of patients with scleroderma.
A 72-h exposure to interferon-gamma reduced procollagen mRNA levels in the scleroderma fibroblast lines to the levels exhibited by the unaffected control fibroblasts.