C-reactive protein (CRP) is a liver-derived acute phase reactant that is a clinical marker of inflammation associated with poor cancer prognosis. Elevated CRP levels are observed in many types of cancer and are associated with significantly increased risk of metastasis, suggesting that CRP could have prometastatic actions. In this study, we reported that CRP promotes lung metastasis by dampening the anticancer capacity of pulmonary macrophages in breast cancer and melanoma. Deletion of CRP in mice inhibited lung metastasis of breast cancer and melanoma cells without significantly impacting tumor growth compared with wild-type mice. In addition, the lungs of CRP-deficient mice were enriched for activated pulmonary macrophages, which could be reduced to the level of wild-type mice by systemic administration of human CRP. Mechanistically, CRP blocked the activation of pulmonary macrophages induced by commensal bacteria in a FcγR2B-dependent manner, thereby impairing macrophage-mediated immune surveillance to promote the formation of a premetastatic niche in the lungs of tumor-bearing mice. Accordingly, treatment with specific CRP inhibitors activated pulmonary macrophages and attenuated lung metastasis in vivo. These findings highlight the importance of CRP in lung metastasis, which may represent an effective therapeutic target for patients with advanced solid cancers in clinics. Significance: CRP maintains host–commensal tolerance by inhibiting pulmonary macrophage activation and can be targeted to remodel the premetastatic niche in the lung to lower the risk of cancer metastasis. See related commentary by Saal et al., p. 4121

Metabolic dysfunction-associated steatotic liver disease (MASLD) has recently been proposed as an alternative term to NAFLD. MASLD is a globally recognized chronic liver disease that poses significant health concerns and is frequently associated with obesity, insulin resistance, and hyperlipidemia. To better understand its pathogenesis and to develop effective treatments, it is essential to establish suitable animal models. Therefore, attempts have been made to establish modelling approaches that are highly similar to human diet, physiology, and pathology to better replicate disease progression. Here, we reviewed the pathogenesis of MASLD disease and summarised the used animal models of MASLD in the last 7 years through the PubMed database. In addition, we have summarised the commonly used animal models of MASLD and describe the advantages and disadvantages of various models of MASLD induction, including genetic models, diet, and chemically induced models, to provide directions for research on the pathogenesis and treatment of MASLD.

Porcine reproductive and respiratory syndrome virus (PRRSV) induces secretion of high mobility group box 1 (HMGB1) to mediate inflammatory response that is involved in the pulmonary injury of infected pigs. Our previous study indicates that protein kinase C-delta (PKC-delta) is essential for HMGB1 secretion in PRRSV-infected cells. However, the underlying mechanism in HMGB1 secretion induced by PRRSV infection is still unclear. Here, we discovered that the phosphorylation level of HMGB1 in threonine residues increased in PRRSV-infected cells. A site-directed mutagenesis study showed that HMGB1 phosphorylation at threonine-51 was associated with HMGB1 secretion induced by PRRSV infection. Co-immunoprecipitation (co-IP) of HMGB1 failed to precipitate PKC-delta, but interestingly, mass spectrometry analysis of the HMGB1 co-IP product showed that PRRSV infection enhanced HMGB1 binding to ribosomal protein S3 (RPS3), which has various extra-ribosomal functions. The silencing of RPS3 by siRNA blocked HMGB1 secretion induced by PRRSV infection. Moreover, the phosphorylation of HMGB1 at threonine-51 was correlated with the interaction between HMGB1 and RPS3. In vivo, PRRSV infection also increased RPS3 levels and nuclear accumulation in pulmonary alveolar macrophages. These results demonstrate that PRRSV may induce HMGB1 phosphorylation at threonine-51 and increase its interaction with RPS3 to enhance HMGB1 secretion. This finding provides insights into the pathogenesis of PRRSV infection.