Genes regulating oxidative-inflammatory response in circulating monocytes and neutrophils in septic syndrome

Elloumi, Nesrine and Bahloul, Mabrouk and Benabdallah, Emna and Kharrat, Sana and Fakhfakh, Raouia and Bouchaala, Karama and Abida, Olfa and Chtara, Kamilia and Masmoudi, Hatem and Bouaziz, Mounir (2023) Genes regulating oxidative-inflammatory response in circulating monocytes and neutrophils in septic syndrome. BIOLOGIA FUTURA, 74 (1-2). pp. 199-207. ISSN 2676-8615 (print); 2676-8607 (online)

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Abstract

Despite significant progress in the past decades, sepsis still lacks a specific treatment. Under normal conditions, leucocytes play a critical role in controlling infection and it is suggested that their activity is impaired during sepsis which contribute to the dysregulation of immune reactions. Indeed, in response to infection, several intracellular pathways are affected mainly those regulating the oxidative- inflammatory axis. Herein, we focused on the contribution of NF-kB, iNOS, Nrf2, HO-1 and MPO genes in the pathophysiology of septic syndrome, by analyzing the differential expression of their transcripts in circulating monocytes and neutrophils, and monitoring the nitrosative/oxidative status in septic syndrome patients. Circulat- ing neutrophils of septic patients displayed a significant overexpression of NF-kB compared to other groups. In monocytes, patients with septic shock expressed the highest levels of iNOS and NF-kB mRNA. However, genes involved in cytoprotec- tive response had increased expression in patients with sepsis, in particular, the Nrf2 and its target gene HO-1. Moreover, patient monitoring indicates that the iNOS enzyme expression and NO plasma levels may play a role in assessing the severity of septic conditions. Overall, in either monocytes or neutrophils, we pointed out the major role of NF-κB and Nrf2 in the pathophysiological process. Therefore, therapies targeted to redox abnormalities may be useful for better management of septic patients.

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