Mechanistic insight into the synergism of IL-27 and IL-28B in regulation of benzo(a)pyrene-induced lung carcinogenesis associated ROS/NF-κB/NLRP3 crosstalk. (25th February 2022)

• Record Type: Journal Article
• Authors: Majumder, Debabrata; Sarkar, Chaitali; Debnath, Rahul; Tribedi, Prosun; Maiti, Debasish
• Is Part Of: Chemico-biological interactions. Volume 354(2022)
• Publication Date: 2022-02-25
• Subjects: Benzo(a)pyrene -- Lung cancer -- NLRP3 -- Mast cell -- PPARγ; AHH Aryl hydrocarbon hydroxylase -- ASC apoptosis-associated speck-like protein containing a caspase-containing domain -- BaP Benzo(a)pyrene -- HIF1α Hypoxia inducible factor 1 alpha -- IL-1β Interleukin 1 beta -- IL-6 Interleukin 6 -- NF-κB Nuclear factor kappa B -- NLRP3 NOD-like receptor protein 3 -- NK cell Natural killer cell -- PPAR Peroxisome proliferator-activated receptor; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2022.109807
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Aim: Our previous work depicted that benzo( a )pyrene (BaP)-induced lung cancer associated pulmonary redox imbalance and inflammation were effectively regulated by the combinatorial treatment of IL-27 and IL-28B. So in continuation of that finding the present study was designed to reveal the inflammation regulating signaling network modulated by IL-27 and IL-28B treatment related to BaP-induced lung cancer. Methods: Male Swiss albino mice were treated with BaP to induce lung tumor. Then they received individual as well as combinatorial treatment of IL-27 and IL-28B. At the end of the experimental schedule, the expression of NF-κB signaling proteins, the formation of NLRP3 inflammasome complex and IL-18; IL-17A expression in the lung were observed using Western blot and RT-PCR. The tissue and serum levels of some proinflammatory cytokines were also studied using ELISA. Mast cell density was also studied using toluidine blue staining procedure. Results: Treatment with IL-27 or IL-28B alone was successful to regulate the expression of NF-κB signaling proteins and NLRP3 complex in some cases but best attenuation was observed in animals who received both IL-27 and IL-28B in combination. In combination, it was successful in down-regulating the expression of p -ERK1/2 and in reducing the accumulation of mast cells in the lung tissue associated with BaP-induced lung carcinogenesis. The impaired PPARγ expression was also reinstated upon combination treatment. Conclusion: Altogether, the treatment in combination with IL-27 and IL-28B is an effective regimen to attenuate the ROS/NF-κB/NLRP3 axis associated with BaP-induced lung carcinogenesis. Highlights: IL-27 + IL-28B restricted the nuclear translocation of NF-κB in lung cancer. IL-27 + IL-28B down-regulated NLRP3 complex formation. PPARγ expression was reinstated upon IL-27 + IL-28B treatment.