
-   High fat diet induced SLPI expression in mice adipose tissue, where it functions to counteract adipocyte inflammation via a mechanism that included stabilization of cellular IKBalpha expression [PMID: 21356117].
-   SLPI expression was highly upregulated in psoriatic skin and healing wounds [PMID: 9856807]. Also in severe udder cleft dermatitis (UCD) lesions in Holstein-Friesian cows [PMID: 37486897]. This is likely mediated through its diverse roles in the innate defense mechanism of the host skin, ranging from anti-protease capacities for protection of matrix fibers, to anti-viral [PMID: 9242546, PMID: 35062299], anti-bacterial functions [PMID: 9856807] and regulating nerve reflex-mediated skin barrier function [PMID: 35279880].
-   Increased mRNA levels of SLPI in calcified aortic valve samples [PMID: 37264340] is likely related to its critical role in modulating osteoblast differentiation and proliferation [PMID: 33837198].
-   mRNA and protein expression levels of SLPI were significantly down-regulated in Hepatocellular carcinoma (HCC) tissues and hepatoma cell lines and low level of SLPI predicted worse survival in our HCC cohorts. Mechanistic studies demonstrated that SLPI played a protective role in HCC progression by enhancing ER stress-induced apoptosis in HCC cells mediated by MAPK signaling pathways [PMID: 34975323]. There are also studies showing SLPI is upregulated in human HCC tissues compared to normal liver tissues, based on data from the TCGA database. This upregulation is linked to altered DNA methylation status around the transcription start site (TSS) of these genes [PMID: 29566670].
-   Down-regulation of SLPI in COPD and cystic fibrosis (CF) is likely mediated via activation of TGF-beta1 signaling under the hypoxia condition [PMID: 18375249, PMID: 25851169], as well as proteolytic cleavage of the protein by neutrophil elastase [PMID: 21349930, PMID: 19912665, PMID: 23024024, PMID: 20007580].

## Summary

The SLPI gene encodes the secretory leukocyte protease inhibitor, which serves as a multipotent defense factor in the colon by inhibiting protease enzymes such as trypsin, chymotrypsin, and elastase, thereby preventing tissue damage. Its inhibitory action on these enzymes is crucial for maintaining the integrity of epithelial surfaces during inflammatory states and for providing antimicrobial activity against specific pathogens such as mycobacteria. [CS: 9]

In the context of colon diseases and toxicities, SLPI is upregulated in response to inflammatory stimuli and microbial infections, fulfilling its function in the protection of epithelial tissues. [CS: 8] For instance, a strong antibacterial response, such as that elicited by murine prion protein (moPrP) in the presence of detoxified lipopolysaccharide, results in overexpression of Slpi mRNA. [CS: 5] This increase in Slpi can be interpreted as the body's attempt to enhance mucosal defenses against bacterial invasion and to modulate local inflammation. [CS: 7] Similarly, in ulcerative colitis (UC), increased expression of SLPI helps to manage the destructive effects of dysregulated protease activity characteristic of UC inflammation. [CS: 8] Likewise, during bacterial infection by pathogens like Clostridium difficile, SLPI is upregulated to provide a protective response against the bacteria's pathogenicity, contributing to the host's innate defense and facilitating the maintenance of colonic homeostasis. [CS: 7]
