Hydrogen sulfide induces the synthesis of proinflammatory cytokines in human monocyte cell line U937 via the ERK-NF-κB pathway

Abstract

Hydrogen sulfide (H2S) is now considered an endogenous, gaseous mediator, which has been demonstrated to be involved in many inflammatory states. However, the mechanism of its proinflammatory function remains unknown. In the present study, we used IFN-gamma-primed human monocytic cell line U937 to investigate the effects of H2S in vitro on monocytes. We found that treatment with the H2S donor, sodium hydrosulfide, led to significant increases in the mRNA expression and protein production of TNF-alpha, IL-1beta, and IL-6 in U937 cells. H2S-triggered monocyte activation was confirmed further by the up-regulation of CD11b expression on the cell surface. We also observed that H2S could induce a rapid degradation of IkappaBalpha and subsequent activation of NF-kappaB p65, and this effect was attenuated by Bay 11-7082, a specific inhibitor of NF-kappaB. Furthermore, pretreatment of cells with Bay 11-7082 substantially inhibited the secretion of TNF-alpha, IL-1beta, and IL-6 induced by H2S. We also found that H2S stimulated the phosphorylation and activation of ERK1/2, but not of p38 MAPK and JNK, and pretreatment with PD98059, a selective MEK1 antagonist, could inhibit H2S-induced NF-kappaB activation markedly. Together, our findings suggest for the first time that H2S stimulates the activation of human monocytes with the generation of proinflammatory cytokines, and this response is, at least partially, through the ERK-NF-kappaB signaling pathway.

Exogenous hydrogen sulfide protects H9c2 cardiac cells against high glucose-induced injury by inhibiting the activities of the p38 MAPK and ERK1/2 pathways

“…The ERK1/2 activation has been shown to be increased (42)(43)(44)(45)(46), decreased (22,23,29,(47)(48)(49) or unaltered (50,51) following exposure to H 2 S. In the present study, we provide clear evidence that the activation of ERK1/2 contributes to HG-induced injury in H9c2 cells and that exogenous H 2 S protects H9c2 cells against HG-induced injury by inhibiting ERK1/2 activation, which is supported by our previous study [Dong et al (23)]. Although the mechanisms through which ERK1/2 induces either cell death or survival and the reasons for the differential effects induced by exogenous H 2 S on the activation of ERK1/2 are unclear, it is generally accepted that the duration and magnitude of ERK1/2 activation may be an important factor in determining cell survival or apoptosis (52).…”

(S)-Tetrahydroisoquinoline Alkaloid Inhibits LPS-Induced Arachidonic Acid Release through Downregulation of cPLA2 Expression

“…A recent study showed that MAPKs and NF-κB pathways were involved in LPSinduced up-regulation of cPLA 2 (Luo et al, 2006). Moreover, MAPKs are reported to mediate both cPLA 2 expression, and phosphorylation (Zhi et al, 2007). Several lines of evidence demonstrate that various stimulators beside LPS induce the expression of cPLA 2 through MAPK activation.…”

Substance P enhances NF-κB transactivation and chemokine response in murine macrophages via ERK1/2 and p38 MAPK signaling pathways

“…The transcriptional dependence of MIP-2 and MCP-1 on NF-B was confirmed with a specific NF-B inhibitor, Bay 11-7082. Bay 11-7082 selectively and irreversibly prevents IB␣ phosphorylation, which disrupts NF-B function by sparing IB␣ from proteasomal degradation, thereby permitting it to bind to and inactivate NF-B (33,45). Pretreatment with Bay 11-7082 diminished the chemokine responses induced by SP, which reinforced NF-B as the main transcriptional regulator involved.…”