
-   TLR4 had a role in promoting spontaneous intestinal tumorigenesis by up-regulating cytokine-cytokine receptor interaction and cancer signalling pathways. TLR4-/- inhibited spontaneous intestinal tumorigenesis in ApcMin/+ model mice. In gut tumors, TLR4 dificiency signifiantly decreased the expression of IL6, GM-CSF, IL11, CCL3 and S100A8/9. While these factors was found to increase the viability of colon cancer cell lines and decrease the apoptosis rate of colon cancer cells with irradiation and chemical treatment [PMID: 31650683].

## Summary

The S100A9 gene encodes a calcium- and zinc-binding protein integral to the regulation of inflammatory processes and immune response [CS: 10]. Its functions include neutrophil chemotaxis, adhesion, enhancement of bactericidal activity through Zn(2+) chelation, and activation of the NADPH-oxidase complex, crucial for an effective immune response [CS: 9]. S100A9 also acts as an alarmin, stimulating innate immune cells via receptors like TLR4 and AGER, triggering pro-inflammatory pathways [CS: 9].

In the context of colon diseases and toxicities, S100A9 is often dysregulated, exhibiting increased expression [CS: 8]. This upregulation is a response to inflammatory stimuli and tissue damage [CS: 9]. For instance, in ulcerative colitis, elevated S100A9 levels correlate with intensified inflammation [CS: 8]. Here, S100A9 enhances neutrophil activity and recruits more immune cells to the site, escalating the immune response to counteract the ongoing inflammation [CS: 8]. Similarly, in colorectal cancer, A. mucinipila administration increases S100A9 expression, possibly as a response to the early inflammatory environment, which is a precursor to tumorigenesis [CS: 7]. This increased expression might be a defensive mechanism aimed at controlling microbial populations and responding to tissue damage, even though it may inadvertently contribute to disease progression [CS: 7]. The protein's ability to regulate cell death, act as an oxidant scavenger, and modulate immune responses aligns with these observed patterns of upregulation during colon-related diseases and toxicities, as these functions are essential in managing cellular stress, inflammation, and microbial threats [CS: 8].
