**10. IFN-**γ**, IL-8 and TGF-**β **expressions are downregulated by whey proteins**

The most notable result of cow milk (CM0 whey therapy was the full abolition of interferon gamma (IFN-γ), as shown by extensive research. IFN-γ has a direct anti-proliferative effect on cancer cell lines. Studies have shown that mice lacking IFN-γ or IFN-γ receptor [113] as well as IFN-γ gene knockout (KO) mice grow cancer more quickly [114]. The late colitis stage and early neoplasms are reflected in the mouse examination and sample selection at 12th week. Dextral Sulfate Sodium (DSS) induced colitis was linked to an elevated level of IFN-γ, which was linked to decrease in weight and more death ratio [115]. Thus, the decreased IFN-γ amount results in the prohibition of immune cell recruitment to the inflammatory region and more tissue harm can clarify CM-mediated inhibition of inflammation. As a result, the neoplasm formation in CM-treated mice may have been influenced by lower mucosal inflammation. In a related vein, it has been shown that CM therapy reduced IFN-γ levels in chronic hepatitis B patients [116].

*Bio-Molecular Characteristics of Whey Proteins with Relation to Inflammation DOI: http://dx.doi.org/10.5772/intechopen.99220*

IL-8 has been shown to play a multifunctional role in cancer development, including encouraging tumor cell proliferation, improving cancer cell survival, and controlling adhesion and invasion [117]. Findings showed that cow milk (CM) significantly reduced IL-8 expression in colon tissue, suggesting that these results may reflect CM's anti-inflammatory mechanism. It was found in a report on immunomodulatory function of milk proteins that IL-8 was recruited by Caco2 gut cells lined with the both α-lactalbumin and β-lactoglobulin of a non-fat bovine milk (BM) whey [118]. This phenomenon occurred by the activation of Caco2 cells by IL-1β. However, it is still needs to be confirmed that either the abstinence of β-LG in CM whey has any link to drop the IL-8 scale or graph in the CM treated population in model. Many studies have shown that all milk ingredients have a synergistic role in lowering IL-8 gene expression [118].

In addition, milk whey treatment reduced transforming growth factor (TGF-β) expression. TGF-β, a cytokine has double role in cancer growth and alteration in the TGF-β pathway within epithelial cells, promotes the enlargement and evolution of colonic tumors [118]. TGF-β signaling in tumor-infiltrating T-lymphocytes, on the other hand, led to the growth of dysplastic epithelial cells in experimental colorectal cancers (CRCs), according to contradictory findings [119]. Varying results on the role of TGF-β in CRC models could be described by the phase of cancer studied or the signaling pathway targeted by the cytokine in specific immune cells.

### **11. Conclusions**

An interesting and verified phenomenon of bovine milk whey proteins is that they are known to act as anti-inflammatory and immune-stimulatory agents in connection with inflammatory and metabolic disorders.

According to molecular hypothesis, whey proteins decrease inflammatory cytokines (IL-1α, IL-1β, IL-10, and TNF-α) by molecularly inhibiting ACE and NF-κB expression, promoting Fas signaling, and increasing caspase-3 expression, while elevating GLP-1, PYY, CCK, GIP, and leptin, as well as chelating and binding iron, manganese, and zinc.

In this chapter, we have described about whey proteins' essential significance in the molecular mechanisms associated with inflammatory health conditions. Whey protein also possesses many other impacts on different health issues on molecular level.

#### **Acknowledgements**

Authors acknowledge the role Food and Nutrition Society Gilgit Baltistan Pakistan for giving free access to journals.

#### **Conflict of interest**

Authors declare no conflict of interest.

#### **Notes/thanks/other declarations**

Authors pay special thanks to everyone for contribution.
