Role of MAP Kinase‐Dependent Apoptotic Pathway in Innate Immune Responses and Viral Infection

Abstract

Mitogen-activated protein (MAP) kinase cascades are multifunctional signalling networks that influence cell growth, differentiation, apoptosis and cellular responses to stress. Apoptosis signal-regulating kinase 1 (ASK1) is a MAP kinase kinase kinase that triggers apoptogenic kinase cascade leading to the phosphorylation/activation of c-Jun N-terminal kinases (JNK) and p38-MAP kinase, which are responsible to induce apoptotic cell death. This pathway plays a pivotal role in the transduction of signals from different apoptotic stimuli. Recently, it has become evident that ASK1 and its downstream pathway are employed in the transduction of signals from Toll-like receptors (TLR) -multistep processes that interfere with different intracellular signalling pathways. TLR are the key proteins that allow mammals to detect pathogens and mediate innate immune responses. In addition, ASK1 and its downstream pathway play a target role in the regulation of apoptosis in some cases of viral infection -AIDS, influenza, hepatitis C and others. In the present review, we summarize current knowledge about the role of ASK1 and its downstream pathway in innate immune responses and viral infection.

Apoptosis‐induced inhibition of CD1d‐mediated antigen presentation: different roles for caspases and signal transduction pathways

“…Ceramide has been shown to induce apoptosis through the activation of MAPK, 13,40 and inhibitors of the p38 and ERK1/2 MAPK pathways reduce it. 13 In line with that work, we found that treatment of cells with a p38-specific inhibitor substantially reversed the PPMP-induced reduction in antigen presentation by CD1d; however, the addition of an ERK1/2 pathway inhibitor did not.…”

Astragali Radix elicits anti-inflammation via activation of MKP-1, concomitant with attenuation of p38 and Erk

“…In response to inflammatory signals including microbial or viral infection, UV-irradiation, and burning, the MAP kinase cascade is activated through phosphorylation of p38, Erk1/2, and JNK, together with activation of NF B (Sumbayev and Yasinska, 2006). This MAP kinase activation is terminated, and returns to base levels within several hours, following its stimulation (Pouyssegur et al, 2002).…”

Caspase 3-Dependent Cell Death of Neurons Contributes to the Pathogenesis of West Nile Virus Encephalitis

“…Apoptosis can act as an innate defense that restricts viral spread by eliminating infected cells and triggering pathogen recognition pathways (58). Alternatively, cell death could directly contribute to the spread and replication of WNV.…”