In addition to the profibrotic role of interleukin 6 and transforming growth factor-β, newer studies stress on glycoprotein Krebs von den Lungen-6 (KL-6), surfactant protein-D (SP-D) and chemokine (C-C motif) ligand 18 (CCL18) as potential biomarkers of skin and lung fibrosis in SSc.<b>Expert opinion</b>: Skin and lung biomarkers in SSc frequently mirror the typical signs of fibrosis, overlapping sporadically.
Here, we found that BLM-induced lung fibrosis with thickened interstitial lung tissue, including fibronectin and collagen, was correlated with the increased serum concentrations of IL-6 and IL-33 and accompanied by reduced lung function, including FRC (functional residual capacity), C chord (lung compliance), IC (inspiratory capacity), VC (vital capacity), TLC (total lung capacity), and FVC (forced vital capacity) (<i>p</i> < 0.05).
Hesperidin alleviates BLM-induced IPF via inhibition of TGF-β1/Smad3/AMPK and IκBα/NF-κB pathways which in turn ameliorate the modulation of oxido-inflammatory markers (Nrf2 and HO-1) and pro-inflammatory markers (TNF-α, IL-1β, and IL-6) to reduce collagen deposition during pulmonary fibrosis.See also Figure 1(Fig.1).
Collectively, IkBα-NFkB signaling activation by Hsp27, which resulted in the facilitation of Twist, IL1β, and IL6 expression, is involved in the EMT process that is tightly connected to the development of IR-induced lung fibrosis.
In vivo, intratracheal treatment with Lv-miR-29c significantly increased expression of miR-29c, and reduced expression of β-catenin, matrix metalloproteinase (MMP)-2, and MMP-9 in the lung and levels of transforming growth factor-beta 1 (TGF-β1) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid, and notably attenuated pulmonary fibrosis as evidenced by hydroxyproline content in silica-administered mice.
Fibrosis-related cytokines interleukin-6 (IL-6) and myofibroblast markers type 1 collagen α1 (COL1A1) levels in supernate of MLF, serum, and bronchoalveolar lavage fluid (BALF) as well as malondialdehyde (MDA) in serum and BALF were detected by ELISA, reactive oxygen species (ROS) generation was measured by 2',7'- dichlorofluorescin diacetate (DCFH-DA) assay and lung pathological/morphological alterations in mice were observed by HE and Masson to assess the antioxidant mechanism and therapeutic effects on pulmonary fibrosis induced by bleomycin.
In conclusion, the gp130 cytokines IL-6 and OSM contribute to the accumulation of profibrotic macrophages and enhancement of bleomycin-induced lung fibrosis.
Atomic layer deposition coating of carbon nanotubes with aluminum oxide alters pro-fibrogenic cytokine expression by human mononuclear phagocytes in vitro and reduces lung fibrosis in mice in vivo.
In vitro activation of IL-6 trans signaling enhanced fibroblast proliferation and extracellular matrix protein production, effects relevant in the progression of pulmonary fibrosis.
In vitro studies disclosed that Calpeptin reduced (i) production of IL-6, TGF-β1, angiopoietin-1 and collagen synthesis from lung fibroblasts; and (ii) both IL-6-dependent proliferation and angiopoietin-1-dependent migration of the cells, which could be the mechanism underlying the preventive effect of Calpeptin on pulmonary fibrosis.
There were significant differences in cytokine (IL-8, IL-1beta, IL-6, TNF-alpha, IL-12) levels of BAL fluid between patients with PF and healthy controls.
We have recently reported that IL-6 and TGF-beta(1) plays an important role in proliferation and differentiation of lung fibroblasts, and all-trans-retinoic acid (ATRA) prevented bleomycin-induced lung fibrosis through the inhibition of these cytokines.
Interleukin-6 (IL-6) is an important immunoregulatory cytokine that has been implicated in a number of fibrotic autoimmune diseases such as scleroderma, interstitial nephritis, and pulmonary interstitial fibrosis.
Furthermore, elevated IL-6 levels were found in bronchoalveolar lavage fluids from patients diagnosed with lung fibrosis and work-related histories of long term asbestos exposure.
These histopathologic changes induced by the transforming growth factor beta 1 and platelet-derived growth factor B gene are partly akin to those changes seen in lung tissues from patients with pulmonary fibrosis and markedly contrast with the changes induced by overexpression of the IL-6 and IL-6 receptor genes that mimics lymphocytic interstitial pneumonia.