TNF-α and IL-10 Control CXCL13 Expression in Human Macrophages

Abstract

The chemokine CXCL13 controls the normal organization of secondary lymphoid tissues and the neogenesis of ectopic lymphoid structures in nonlymphoid organs, particularly the lungs.The progression and severity of idiopathic pulmonary fibrosis (IPF), a fatal and irreversible interstitial lung disease, is predicted by the circulating blood concentrations of CXCL13.While CXCL13 is produced by pulmonary tissues, it has not been determined which cells are involved. This study examines CXCL13 production by lung tissue macrophages from patients with IPF and the signaling pathways controlling CXCL13 gene expression in human alveolar macrophages (AM) and monocyte-derived macrophages (MoDM). CXCL13 is found in CD68-and CD206-positive AM from patients with IPF, and the CXCL13 gene is induced in these macrophages and MoDM when they are stimulated with lipopolysaccharide. We found that TNF- and IL-10 control optimal CXCL13 gene expression in MoDM and possibly in AM by activating the NF-B and JAK/STAT pathways, respectively. We also found that blood TNF- and CXCL13 concentrations are significantly correlated in patients with IPF, suggesting that TNF- contributes to CXCL13 production in humans. In conclusion, the results of this study demonstrate that AM from patients with IPF produces CXCL13 and that the NF-B and JAK/STAT pathways are required to induce the expression of this major chemokine.

Biomimetic Nanoparticles Potentiate the Anti-Inflammatory Properties of Dexamethasone and Reduce the Cytokine Storm Syndrome: An Additional Weapon against COVID-19?

“…It is worth noting that these chemokines are mainly involved in pulmonary inflammation in COVID-19 patients [25]. They have been associated with an increased inflammatory response at the level of airway epithelial cells and macrophages, and with chemotactic activity towards B and T cells [26]. Lastly, we observed a reduction in the terminal complement effector C5 in the group treated with DEX-LKs (Figure 5).…”

Long-Term Release of Dexamethasone With a Polycaprolactone-Coated Electrode Alleviates Fibrosis in Cochlear Implantation

“…Previous studies have shown that the activation of myofibroblasts and the production of extracellular matrix induced by the production of TGF-β1 by macrophages are key links in the process of fibrosis in other organs (Wynn and Ramalingam, 2012). After uncoated electrode implantation, macrophages migrate to the surface of the electrode (Bellamri et al, 2019). Foreign body reactions can lead to the degradation of CI biomaterials.…”

Combined anti-fibrotic and anti-inflammatory properties of JAK-inhibitors on macrophages in vitro and in vivo: Perspectives for scleroderma-associated interstitial lung disease

“…Protein extracts were prepared as previously described (21) (Fig. 6) was performed using Microsoft ® Excel (V16.16.19) .…”

“…These potential unbalanced anti-inflammatory and anti-fibrotic properties of JAK inhibitors on macrophages could be especially important in the context of diseases characterized by concomitant inflammatory and fibrotic manifestations (20). Interstitial lung disease (ILD) and especially connective tissue disease/autoimmune disorders-associated ILD, are characterized by such combinations of pro-inflammatory and pro-fibrotic phenomena (20,21,22). ILD is a class of heterogeneous pulmonary disorders that involves the association of an infiltrate of mononuclear cells, especially including lung macrophages, with fibrotic features characterized by collagen depositions in the interstitial compartment and, in some cases, in the bronchial and/or alveolar lumen.…”