Fig. 5: IL-6 mediates the pro-fibrotic response of JUN involvement.

a The secreted proteins in the lung bronchoalveolar lavage (BAL) of 4 fibrotic lung patients were quantified by Luminex assay, showing IL-6 as the highest expressed cytokine across all fibrotic patient BAL samples. Data were normalized by protein levels of the BAL of 3 normal lungs, and presented as mean ± SD. b Cytokines and chemokines in the fibrotic mouse bronchoalveolar lavage (BAL) after JUN induction were quantified by Luminex assay, and detected IL-6 was consistently among the most highly expressed cytokines in JUN-induced mouse fibrotic lungs indicative of IL-6-JAK-STAT pathway activation. Data were normalized by normal lung expression, and presented as mean ± SD, n = 3. c The cytokines/chemokines released from JUN-induced lung fibrotic mice-derived whole bone marrow (n = 4), fibroblasts (n = 4) and monocytes/macrophages (n = 3) in the medium after 48 h of Dox-initiated JUN induction were quantified by Luminex assay, demonstrating that whole bone marrow and fibroblasts are secreting increased IL-6 in response to JUN. Data were presented as mean ± SD. d Increased IL-6 expression levels were detected by Taqman assay and Flow cytometry in primary lung fibroblasts with JUN knockout (KO) or overexpression (OE). Data are expressed as mean ± SD from 4 experimental repeats. Two-tailed ratio paired t-test, ***P < 0.001. e, f IL-6 increased CD47 enhancer activity at concentrations as low as 1 ng/ml (e) and protein expression at 10 ng/ml (f) in a dose-dependent fashion. Data are expressed as mean ± SD from three independent experiments, ordinary one-way ANOVA with multiple comparisons test, n.s. non-significant; **P < 0.01; ***P < 0.001. See Supplementary Data 2 for statistical details. Source data are provided as a Source Data file.