Resistin Expression Is Associated With Interstitial Lung Disease in Dermatomyositis

Abstract

ObjectiveIn the current study, we aimed to assess resistin mRNA levels in the peripheral blood mononuclear cells (PBMCs) of dermatomyositis patients with interstitial lung disease (DM-ILD) and their correlation with disease activity.MethodsWe detected resistin mRNA levels in the PBMCs of 37 DM-ILD, 8 DM patients without ILD, and 19 healthy control (HC) subjects by performing quantitative reverse transcription real-time polymerase chain reaction analysis. Associations between resistin expression levels and major clinical manifestations, laboratory examinations, and disease activity were also analyzed. In addition, resistin expression in lung specimens from patients with DM-ILD was examined via immunohistochemistry and immunofluorescence.ResultsResistin mRNA levels in PBMCs were significantly higher in DM-ILD than that in DM patients without ILD and HCs (p = 0.043, 0.014, respectively). Among these DM-ILD patients, the resistin levels were significantly elevated in those with rapidly progressive ILD than in those with chronic ILD (p = 0.012). The resistin mRNA levels in DM-ILD positively correlated with serum alanine aminotransferase (r = 0.476, p = 0.003), aspartate aminotransferase (r = 0.488, p = 0.002), lactate dehydrogenase (r = 0.397, p = 0.014), C-reactive protein (r = 0.423, p = 0.008), ferritin (r = 0.468, p = 0.003), carcinoembryonic antigen (r = 0.416, p = 0.011), carbohydrate antigen 125 (r = 0.332, p = 0.047), interleukin-18 (r = 0.600, p < 0.001), and lung visual analog scale values (r = 0.326, p = 0.048), but negatively correlated with the diffusing capacity of carbon monoxide (DLco)% (r = −0.447, p = 0.041). Immunohistochemical analysis of resistin showed its elevated expression in the macrophages, alveolar epithelial cells, and weak fibrotic lesions from patients with DM-ILD. Immunofluorescence staining confirmed CD68+ macrophages co-express resistin.ConclusionsResistin levels were increased in patients with DM-ILD and associated with disease activity and ILD severity. Therefore, resistin may participate in the pathogenesis of DM-ILD and may act as a useful biomarker.

The Role of Macrophages in Connective Tissue Disease-Associated Interstitial Lung Disease: Focusing on Molecular Mechanisms and Potential Treatment Strategies

“…Acting via nuclear factor kappa B (NFκB) signaling, resistin upregulates IL-1, IL-6, and TNF-α in human monocytes. These proinflammatory cytokines induce resistin expression in macrophages (Figure 2), triggering a self-sustained loop for lung injury [85]. Together, these studies highlight the contribution of macrophages to DM-ILD.…”

Linking Adiposity to Interstitial Lung Disease: The Role of the Dysfunctional Adipocyte and Inflammation

“…SSc patients with ILD had higher resistin levels compared to healthy controls without ILD [ 53 ]. In dermatomyositis-associated ILD, patients with higher resistin levels also had decreased DLCO and more often had a rapidly progressive ILD [ 54 ]. Elevated resistin levels in adiposity may partially explain increased risk for a variety of different types of ILD.…”

“…Resistin is another adipokine that has been linked to the development of systemic sclerosis-associated ILD [ 52 ]. In mice, resistin is mainly produced in adipocytes, although in humans it is also produced by peripheral mononuclear cells, macrophages, and myeloid cells [ 54 ]. Resistin promotes the production of several inflammatory cytokines, including IL-6, IL-1β, TNF-α, and IL-12 [ 53 , 54 ].…”

“…In mice, resistin is mainly produced in adipocytes, although in humans it is also produced by peripheral mononuclear cells, macrophages, and myeloid cells [ 54 ]. Resistin promotes the production of several inflammatory cytokines, including IL-6, IL-1β, TNF-α, and IL-12 [ 53 , 54 ]. Various damage signals that lead to a T helper 2 (Th2) response may increase resistin expression, with resistin creating a positive feedback loop, leading to further activation of damage-associated molecular patterns (DAMPs) [ 94 ].…”