Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6C macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed. Results showed a marked activation of IL-6/STAT3 signaling by stress. The detrimental action of stress was not terminated in IL-6 mice. Interestingly, the composition of gut microbiota was dramatically changed after stress, with expansion of inflammation-promoting bacteria. Furthermore, results showed stress-induced deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. Of note is that, in the case of cohousing, the stress-induced immune reaction and decreased body weight were abrogated, and transferred gut microbiota from stressed mice to control mice was sufficient to facilitate DSS-induced colitis. The important role of gut microbiota was further reinforced by broad-spectrum antibiotic treatment. Taken together, our results reveal that chronic stress disturbs gut microbiota, triggering immune system response and facilitating DSS-induced colitis.

Graphical abstract A proposed model illustrating the therapeutic effect of QCT on AKI. QCT inhibits the expression of ATF3. While ATF3 blocks the system Xc-, and then suppresses GPX4, inducing ferroptosis. In another side, ferroptotic cells secrete chemokines like CCL2, CCL7, induce the recruitment of macrophages, and then cause the inflammation in AKI. In summary, QCT ameliorates AKI through the inhibition on ferroptosis and the following inflammation.

No abstract

No abstract

No abstract

Depression drives cancer progression and induces poor clinical outcome. However, the mechanisms underlying depression and cancer outcomes are unclear. In this work, we investigated 98 prostate cancer patients and found that patients with high score of psychological depression were correlated with tumor invasion and metastasis. We found focal adhesion kinase (FAK) was increased in cancer patients with metastatic features and high score of depression. FAK knockdown completely blocked depression-promoted tumor invasion in orthotopic transplantation tumors. In Hi-myc mice and a murine model of depression, sympathetic activation was detected in the prostate tissue. Further we showed that FAK activation was dependent on a cAMP-PKA signaling pathway. Our results demonstrated that the activation of a sympathetic-FAK signaling pathway in prostate cancer patients with high degrees of depression facilitates tumor invasion. We suggest that blocking β2AR with propranolol or inhibiting FAK activation with PF562 271 may be novel strategies for depressed patients with invasive prostate cancer.

Purpose: Psychologic depression has been shown to dysregulate the immune system and promote tumor progression. The aim of this study is to investigate how psychologic depression alters the immune profiles in prostate cancer.Experimental Design: We used a murine model of depression in Myc-CaP tumor-bearing immunocompetent FVB mice and Hi-myc mice presenting with spontaneous prostate cancer. Transwell migration and coculture assays were used to evaluate myeloid cell trafficking and cytokine profile changes evoked by Myc-CaP cells that had been treated with norepinephrine (NE), a major elevated neurotransmitter in depression. Chemoattractant, which correlated with immune cell infiltration, was screened by RNA-seq. The chemoattractant and immune cell infiltration were further confirmed using clinical samples of patients with prostate cancer with a high score of psychologic depression.Results: Psychologic depression predominantly promoted tumor-associated macrophage (TAM) intratumor infiltrations, which resulted from spleen and circulating monocytic myeloid-derived suppressor cell mobilization. Neuropeptide Y (NPY) released from NE-treated Myc-CaP cells promotes macrophage trafficking and IL6 releasing, which activates STAT3 signaling pathway in prostate cancer cells. Clinical specimens from patients with prostate cancer with higher score of depression revealed higher CD68 þ TAM infiltration and stronger NPY and IL6 expression.Conclusions: Depression promotes myeloid cell infiltration and increases IL6 levels by a sympathetic-NPY signal. Sympathetic-NPY inhibition may be a promising strategy for patients with prostate cancer with high score of psychologic depression.See related commentary by Mohammadpour et al., p. 2363

No abstract