p38 MAPK (mitogen-activated protein kinases) family proteins (,
, and ) are key inflammatory kinases and play an
important role in relaying and processing intrinsic and extrinsic signals in
response to inflammation, stress, and oncogene to regulate cell growth, cell
death and cell transformation. Recent studies in genetic mouse models revealed
that p38 in epithelial cells mostly suppresses whereas in immune cells
it promotes inflammation and inflammation-associated oncogenesis. On the
contrary, p38 and p38 signaling in immune and epithelial
cells is both pro-inflammatory and oncogenic. This review summarizes recent
discoveries in this field, discusses possible associated mechanisms, and
highlights potentials of systemically targeting isoform-specific p38 MAPKs.
Understanding of p38 MAPK isoform-specific and cell/tissue- and perhaps
stage-dependent effects and their integrated regulated activity in inflammation
and in inflammation-associated oncogenesis is essential for effectively targeting
this group of kinases for therapeutic intervention.