Abstract
Gap junctions (Gjs), formed by specific protein termed connexins (Cxs), regulate many important cellular processes in cellular immunity. However, little is known about their effects on humoral immunity. Here we tested whether and how Gj protein connexin43 (Cx43) affected antibody production in spleen cells. Detection of IgG in mouse tissues and serum revealed that wild-type (Cx43+/+) mouse had a significantly higher level of IgG than Cx43 heterozygous (Cx43+/−) mouse. Consistently, spleen cells from Cx43+/+ mouse produced more IgG under both basal and lipopolysaccharide (LPS)-stimulated conditions. Further analysis showed that LPS induced a more dramatic activation of ERK and cell proliferation in Cx43+/+ spleen cells, which was associated with a higher pro-oxidative state, as indicated by the increased NADPH oxidase 2 (NOX2), TXNIP, p38 activation and protein carbonylation. In support of a role of the oxidative state in the control of lymphocyte activation, exposure of spleen cells to exogenous superoxide induced Cx43 expression, p38 activation and IgG production. On the contrary, inhibition of NOX attenuated the effects of LPS. Collectively, our study characterized Cx43 as a novel molecule involved in the control of spleen cell activation and IgG production. Targeting Cx43 could be developed to treat certain antibody-related immune diseases.
Highlights
Gap junctions (Gjs) are intercellular channels that directly link the cytoplasm of the adjacent cells
Intercellular communication mediated by Gjs provides a pathway for the intercellular exchange of signaling molecules, which is fundamentally essential for the maintenance of homeostasis in tissues and organs and has been shown to regulate a wide range of cellular processes and functions [1,2]
During our Western blot analysis of the denatured tissue samples from Cx43+/+ and Cx43+/− mice with anti-mouse immunoglobulin G (IgG) antibodies, we noticed two nonspecific bands at the molecular weight of 55 and 25 kDa, which was consistently different between Cx43+/+ and Cx43+/− mice
Summary
Gap junctions (Gjs) are intercellular channels that directly link the cytoplasm of the adjacent cells. They are formed by a specific family of proteins termed connexin (Cx). Docking of two hemichannels in apposed membranes of two neighboring cells forms an intact Gj channel. Connexin (Cx43) has been the focus of many investigations because it is predominantly and ubiquitously expressed in many cell types. Intercellular communication mediated by Gjs provides a pathway for the intercellular exchange of signaling molecules, which is fundamentally essential for the maintenance of homeostasis in tissues and organs and has been shown to regulate a wide range of cellular processes and functions [1,2]
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