Abstract
Inflammation is a complex defensive response activated after various harmful stimuli allowing the clearance of damaged cells and initiating healing and regenerative processes. Chronic, or pathological, inflammation is also one of the causes of neoplastic transformation and cancer development. MAP17 is a cargo protein that transports membrane proteins from the endoplasmic reticulum. Therefore, its overexpression may be linked to an excess of membrane proteins that may be recognized as an unwanted signal, triggering local inflammation. Therefore, we analyzed whether its overexpression is related to an inflammatory phenotype. In this work, we found a correlation between MAP17 expression and inflammatory phenotype in tumors and in other inflammatory diseases such as Crohn's disease, Barrett's esophagus, COPD or psoriasis. MAP17 expression correlated also with the markers of inflammation HLAs, BBS10, HERC2, ADNP and PYCARD. Furthermore, we found that MAP17 expression directly regulates NFAT2 and IL-6 activation, inducing the differentiation of monocytes to dendritic cells and suggesting a causal role of MAP17 in inflammation. Immunohistochemistry confirms local inflammation, mainly CD45+ cells, at the site of expression of MAP17, at least in tumors, Crohn's and psoriasis. Therefore, our data indicates that the overexpression of the protein MAP17 plays important role in diseases involving chronic inflammation.
Highlights
Inflammation is a common defensive response that is activated after different harmful stimuli
According to our results, MAP17 triggers the attraction of inflammatory cells by increasing protein membrane loading and modifies the expression of genes connected to inflammation, showing a clear induction of the inflammatory profile
Within the list of genes related to MAP17 expression, there are numerous genes involved in the inflammasome; inflammatory pathwayrelated genes positively correlated with MAP17
Summary
Inflammation is a common defensive response that is activated after different harmful stimuli It is a highly complex biological mechanism that allows the clearance of damaged cells and the removal of pathogens, initiating healing and regenerative processes [1, 2]. When the inflammatory cells are incapable of eliminating the pathogen, inflammation may turn chronic, being characterized by a high level of leukocyte infiltration in damaged tissues. This chronic inflammatory condition contributed to the origin of many syndromes, including Crohn’s disease, lupus, psoriasis and www.impactjournals.com/oncotarget atherosclerosis. It has been connected to Alzheimer’s disease and cardiovascular disease [7, 8]
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