Negative Regulators of Inflammation Response to the Dynamic Expression of Cytokines in DF-1 and MDCK Cells Infected by Avian Influenza Viruses

Abstract

The H5N1 and H9N2 avian in uenza viruses (AIVs) seriously endanger the poultry industry and threaten human health. Characteristic in ammatory responses caused by H5N1 and H9N2 AIVs in birds and mammals result in unique clinical manifestations. The role of anti-in ammatory regulators, PTX3, Del-1 and GDF-15, in H5N1 and H9N2-AIV-mediated in ammation in birds and mammals has not yet been veri ed. Here, the expression of PTX3, Del-1 and GDF-15 in DF-1 and MDCK cells infected with H5N1 and H9N2 AIVs and their effect on in ammatory cytokines were analyzed. Infection with both AIVs increased PTX3, Del-1 and GDF-15 expression in DF-1 and MDCK cells. Infection with H9N2 or H5N1 AIV in DF-1 and MDCK cells with overexpression of all three factors, either alone or in combination, inhibited the expression of tested in ammatory cytokines. Furthermore, co-expression of PTX3, Del-1 and GDF-15 enhanced the inhibition, irrespective of the cell line. The ndings from this study offer insight into the pathogenic differences between H5N1 and H9N2 AIVs in varied hosts. Moreover, our ndings can be used to help screen for host-speci c anti-in ammatory agents.

The Potential Role of Growth Differentiation Factor 15 in COVID-19: A Corollary Subjective Effect or Not?

“…Interestingly, the GDF15 is highly expressed in males as compared to females as it is inversely correlated with testosterone level [ 29 ]. Recently, overexpression of anti-inflammatory GDF15 has been found to reduce the infectivity and severity of H5N1 [ 30 ]. Despite the GDF15 role in both viral and bacterial infections, it induces a protective effect by inducing metabolic tolerance against infection-induced inflammation [ 31 ].…”

Growth Differentiation Factor-15 in Immunity and Aging

“…One recent paper demonstrated that GDF-15 overproduction increases severity of human rhinovirus infections ( Wu et al, 2017 ), and Kleinertz et al reported that GDF-15 levels were increased in injury patients who progressed to sepsis compared to those who did not ( Kleinertz et al, 2019 ). Likewise, GDF-15 expression is increased in cells infected with avian influenza viruses, and this in turn limits their production of cytokines ( Zhao et al, 2021 ). COVID-19 patients have elevated GDF-15 levels ( Notz et al, 2020 ; Rochette et al, 2021 ), suggesting a potential link between GDF-15 and disease severity in the ongoing pandemic.…”