Cadmium exposure induces inflammation through the canonical NF-κΒ pathway in monocytes/macrophages of Channa punctatus Bloch. Issue 110 (March 2021)

• Record Type: Journal Article
• Authors: Choudhury, Chohelee; Mazumder, Ritwik; Biswas, Rajib; Sengupta, Mahuya
• Is Part Of: Fish & shellfish immunology. Issue 110(2021)
• Page Start: 116
• Page End: 126
• Publication Date: 2021-03
• Subjects: Cadmium -- Macrophages -- Cytokines -- Immune response -- iNOS -- NF-κΒ; Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2021.01.002
• Languages: English
• ISSNs: 1050-4648

Abstract

Abstract: A vast range of research related to the toxicity of the heavy metal cadmium (Cd) has been carried out in a wide variety of fish species. However, Cd induced immunomodulation in monocytes/macrophages of Channa punctatus Bloch. has rarely been explored. The present study was designed to determine Cd induced immune response, role of NF-κB (nuclear factor kappa B) pathway and the subsequent downstream molecular responses in monocytes/macrophages of C. punctatus. Fish were sampled and acclimatized, with one group treated with cadmium chloride (CdCl2 ) (1.96 mg/L) and another kept as untreated control group, both under observation for 7 days. Exposure to CdCl2 was found to alter hematological profile of C. punctatus in addition to incurring histo-architectural damages in the HK (head kidney) and ultrastructural changes in the monocytes/macrophages. The innate immune potential was found to be significantly compromised as evident from decreased phagocytosis, intracellular killing, cell adhesion and reduced release of nitric oxide (NO) and myeloperoxidase (MPO) in Cd intoxicated group. Also Cd triggered ROS generation, reduced cellular NO levels by forming peroxynitrite along with the upregulated expression of the inflammatory marker iNOS (inducible nitric oxide synthase) in monocytes/macrophages, both at mRNA and protein levels, indicating inflammation. Inflammation is further verified from the upregulated expression of proinflammatory cytokines viz. TNF-α, IL-1β, IL-6, IL-12 along with a central inflammatory mediator NF-κΒ and downregulation of the anti-inflammatory cytokine IL-10, both at mRNA and protein levels. It can be concluded that, a sub-lethal exposure of Cd in C. punctatus for 7 days caused significant alterations in the hematological, histological and ultrastructural profile in monocytes/macrophages; impaired innate immune parameters, triggers ROS generation and inflammation as validated from the upregulated expression of NF-κΒ, iNOS, TNF-α, IL-1β, IL-6, IL-12 and IL-10 downregulation. Graphical abstract: Image 1 Highlights: Cadmium (Cd) exposure alters blood profile of Channa punctatus Bloch. Cd causes histological changes in HK and ultrastructural alterations in HKM. Cd compromises innate immune potential and trigger ROS generation. Cd upregulates iNOS but reduces NO that reacts with ROS to form peroxynitrite. Cd exposure induces inflammation through canonical NF-κΒ pathway.