Neutrophils are short-lived cells that play a crucial role in inflammation. As in other tissues, these polymorphonuclear phagocytes are involved in the intestinal inflammatory response, on the one hand, contributing to the activation and recruitment of other immune cells, but on the other hand, facilitating intestinal mucosa repair by releasing mediators that aid in the resolution of inflammation. Even though these responses are helpful in physiological conditions, excessive recruitment of activated neutrophils in the gut correlates with increased mucosal damage and severe symptoms in patients with inflammatory bowel disease (IBD) and pre-clinical models of colitis. Thus, there is growing interest in controlling their biology to generate novel therapeutic approaches capable of reducing exacerbated intestinal inflammation. However, the beneficial and harmful effects of neutrophils on intestinal inflammation are still controversial. With this review, we summarise and discuss the most updated literature showing how neutrophils (and neutrophil extracellular traps) contribute to developing and resolving intestinal inflammation and their putative use as therapeutic targets.

Macrophage metalloelastase or matrix metalloproteinase-12 (MMP12) is a macrophage-specific proteolytic enzyme involved in the physiopathology of many inflammatory diseases, including inflammatory bowel disease. Although previously published data suggested that the modulation of MMP12 in macrophages could be a determinant for the development of intestinal inflammation, scarce information is available on the mechanisms underlying the regulation of MMP12 expression in those phagocytes. Therefore, in this study, we aimed to delineate the association of MMP12 with inflammatory bowel disease and the molecular events leading to the transcriptional control of this metalloproteinase. For that, we used publicly available transcriptional data. Also, we worked with the RAW 264.7 macrophage cell line for functional experiments. Our results showed a strong association of MMP12 expression with the severity of inflammatory bowel disease and the response to relevant biological therapies. In vitro assays revealed that the inhibition of mechanistic target of rapamycin complex 1 (mTORC1) and the stimulation of the AMP-activated protein kinase (AMPK) signaling pathway potentiated the expression of Mmp12. Additionally, AMPK and mTOR required a functional downstream glycolytic pathway to fully engage with Mmp12 expression. Finally, the pharmacological inhibition of MMP12 abolished the expression of the proinflammatory cytokine Interleukin-6 (Il6) in macrophages. Overall, our findings provide a better understanding of the mechanistic regulation of MMP12 in macrophages and its relationship with inflammation.

Background. Obesity is associated with an increased risk for different chronic diseases such as osteoarthritis (OA) or rheumatoid arthritis (RA). In fact, adipose tissue is now recognized as an endocrine organ able to secrete a wide variety of factors called adipokines, which have been demonstrated to participate in the pathophysiology of RA by regulating inflammation and immunity. LCN2 is one of these adipose tissue‐derived factors. However, scarce information is available about the levels of this adipokine in different rheumatic diseases. Therefore, we aimed to analyze LCN2 serum levels in healthy, OA, and RA patients under different treatments. Methods. Serum levels of LCN2, among other proinflammatory and chemotactic factors, have been measured by ELISA or Multiplex in the following four groups of individuals: healthy, OA, and RA patients treated with conventional treatment or adalimumab. Results. We found increased serum levels of LCN2 in OA and RA patients. Interestingly, LCN2 serum levels show a similar pattern to that observed for different proinflammatory and chemotactic factors, being increased in RA conventional treated patients in comparison to RA patients treated with adalimumab. Also, RA patients under conventional treatment revealed a positive and significant correlation between LCN2 and CCL2, CCL3, IL‐8, IL‐1β, IL‐6, and CRP. In patients with RA treated with adalimumab, only IL‐6 and CRP correlated significantly with LCN2. Conclusions. Our results clearly suggest that LCN2 is modulated and associated with inflammation in rheumatic diseases. Therefore, the serum levels of this adipokine might be used as an additional biomarker of the inflammatory/disease activity.