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Human filarial proteins attenuate chronic colitis in an experimental mouse model
1Department of Biochemistry & JB Tropical Disease Research Center, Mahatma Gandhi Institute of Medical Sciences, Sevagram, Maharashtra, India.
Abstract:
Encouraged by our earlier results of promising therapeutic effect of filarial recombinant proteins BmALT2, BmCys and WbL2 individually in the mouse model of acute ulcerative colitis, in this study, these proteins have been explored individually and in different combinations for their therapeutic potential in dextran sulphate sodium (DSS)-induced chronic colitis mice. These mice, treated with filarial proteins, showed reduced disease parameters including body weight loss, disease activity index, macroscopic and histopathological scores of colon and myeloperoxidase activity in colonic mucosa. Among various treatment schemes, rBmALT2 + rBmCys which showed most pronounced therapeutic implication was found to downregulate the mRNA expressions of IFN-γ and TNF-α and upregulate IL-10 and TGF-β expression in the splenocytes. Also, increase in level of IgG1 and IgG2a isotypes in the sera of rBmALT2 + rBmCys-treated colitis mice was noted. Activated NF-κB level was found to be reduced in the colon of treated colitis mice compared to untreated one. In conclusion, filarial proteins in combination have been shown to improve the clinicopathologic status of chronic colitis through suppression of pro-inflammatory immune response most possibly in NF-κB-dependent manner. We propose this therapeutic strategy to be tested further to be considered as an effective option in chronic colitis.
Insights
Filarial proteins, particularly BmALT2 and BmCys, show therapeutic potential for chronic colitis by reducing inflammation and improving disease markers. This combination therapy may offer a novel treatment strategy for inflammatory bowel disease.
Area of Science:
- Immunology
- Gastroenterology
- Parasitology
Background:
- Filarial recombinant proteins (BmALT2, BmCys, WbL2) previously showed promise in acute ulcerative colitis models.
- Chronic colitis models require further investigation for effective therapeutic interventions.
Purpose of the Study:
- To evaluate the therapeutic potential of filarial recombinant proteins, individually and in combination, for dextran sulphate sodium (DSS)-induced chronic colitis in mice.
- To elucidate the underlying immune mechanisms modulated by these proteins.
Main Methods:
- Mice with DSS-induced chronic colitis were treated with filarial proteins (BmALT2, BmCys, WbL2) individually and in combinations.
- Disease parameters including body weight loss, disease activity index, and colon histopathology were assessed.
- Immune responses were analyzed by measuring cytokine mRNA expression (IFN-γ, TNF-α, IL-10, TGF-β) in splenocytes, immunoglobulin isotype levels (IgG1, IgG2a) in sera, and NF-κB activation in colonic tissue.
Main Results:
- Filarial protein treatment significantly reduced disease parameters in chronic colitis mice.
- The combination of rBmALT2 + rBmCys demonstrated the most pronounced therapeutic effect.
- This combination downregulated pro-inflammatory cytokines (IFN-γ, TNF-α) and upregulated anti-inflammatory cytokines (IL-10, TGF-β).
- Increased IgG1 and IgG2a levels and reduced NF-κB activation were observed in treated mice.
Conclusions:
- Filarial proteins, especially in combination (rBmALT2 + rBmCys), effectively improve the clinicopathological status of chronic colitis.
- The therapeutic effect is mediated through the suppression of pro-inflammatory immune responses, likely via an NF-κB-dependent pathway.
- This strategy warrants further investigation as a potential treatment for chronic colitis.
