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Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor indicated for the first-line treatment of patients with metastatic or advanced non-small cell lung cancer (NSCLC) whose tumors have specific EGFR mutations. Pulmonary toxicity is one of the fatal adverse effects of gefitinib and the underlying mechanism remains unclear. Here we demonstrated that alveolar macrophages contributed to gefitinib-induced pulmonary toxicity through promoting alveolar epithelial cells to undergo epithelial to mesenchymal transition (EMT) and inducing activation and antiapoptotic effect in fibroblasts. Further, we found that alveolar macrophage-secreted MCP-1 worked as a key factor in the pathologic changes of these two cell types. Gefitinib increased Mcp-1 transcription level via the nuclear import of the transcription factor STAT3. In conclusion, our data uncovered the underlying mechanisms of macrophage-promoted pulmonary toxicity in the presence of gefitinib. MCP-1 antibody or inhibition of STAT3 activation may represent novel therapeutic strategies for preventing gefitinib-induced pulmonary toxicity., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Renal fibrosis is the common final outcome of nearly all progressive chronic kidney diseases (CKD) that eventually develop into end-stage renal failure, which threatens the lives of patients. Currently, there are no effective drugs for the treatment of renal fibrosis. However, studies have shown that certain plant natural products have a fibrosis-alleviating effect. Thus, we have screened a large number of natural products for their ability to protect against renal fibrosis and found that bisdemethoxycurcumin has a good therapeutic effect in renal fibrosis according to the data obtained in a mouse model of unilateral ureteral obstruction (UUO). The results indicate that bisdemethoxycurcumin can efficiently attenuate renal fibrosis induced by UUO. Additional studies of the bisdemethoxycurcumin mechanism of action in the treatment of renal fibrosis demonstrated that the therapeutic effect of bisdemethoxycurcumin is mediated by the specific induction of fibroblast apoptosis at a concentration of 20 μM. bisdemethoxycurcumin can efficiently protect against renal fibrosis both in vitro and in vivo. This discovery will provide new ideas for renal fibrosis treatment in clinics and a new direction for the development of effective drug therapy of renal fibrosis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Idiopathic pulmonary fibrosis is a pathological result of dysfunctional repair response to tissue injury, leading to chronically impaired gas exchange and death. Macrophages are believed to be critical in this disease pathogenesis; However, the exact mechanisms remain enigmatic. Here, we demonstrated that macrophages might contribute to pulmonary fibrosis at the early stage because the aggregation of macrophages appeared earlier than epithelial-mesenchymal transition and fibrosis in mouse and rat experimental models of pulmonary fibrosis. It has been found that macrophages could promote epithelial-mesenchymal transition of alveolar epithelial cells and fibroblast migration in co-culture models between macrophages and alveolar epithelial cells/fibroblasts. Importantly, we used protein micro array to analyze the cytokines that were altered after bleomycin treatment. Only thymic stromal lymphopoietin and matrix metalloproteinase 9 were significantly increased. We further confirmed that TSLP participated in the macrophage-induced epithelial-mesenchymal transition of alveolar epithelial cells using a TSLP recombinant protein. MMP9 was also involved in macrophage-induced fibroblast migration, which can be reversed by an inhibitor of MMP9. Collectively, these findings explained the underlying mechanisms of macrophage-promoted pulmonary fibrosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)