{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T01:10:16Z","timestamp":1777425016174,"version":"3.51.4"},"reference-count":50,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Gastrointestinal and Liver Physiology"],"published-print":{"date-parts":[[2001,10,1]]},"abstract":"<jats:p>Enteropathogenic Escherichia coli (EPEC) alters many functions of the host intestinal epithelia. Inflammation is initiated by activation of nuclear factor (NF)-\u03baB, and paracellular permeability is enhanced via a Ca<jats:sup>2+<\/jats:sup>- and myosin light-chain kinase (MLCK)-dependent pathway. The aims of this study were to identify signaling pathways by which EPEC triggers inflammation and to determine whether these pathways parallel or diverge from those that alter permeability. EPEC-induced phosphorylation and degradation of the primary inhibitor of NF-\u03baB (I\u03baB\u03b1) were tumor necrosis factor (TNF)-\u03b1 and interleukin (IL)-1\u03b2 independent. In contrast to Salmonella typhimurium, EPEC-stimulated I\u03baB\u03b1 degradation and IL-8 expression did not require Ca<jats:sup>2+<\/jats:sup>. Instead, extracellular signal-regulated kinase (ERK)-1\/2 was significantly and rapidly activated. ERK1\/2 inhibitors attenuated I\u03baB\u03b1 degradation and IL-8 expression. Although ERK1\/2 can activate MLCK, its inhibition had no impact on EPEC disruption of the tight junction barrier. In conclusion, EPEC-induced inflammation 1) is TNF-\u03b1 and IL-1\u03b2 receptor independent, 2) utilizes pathways differently from S. typhimurium, 3) requires ERK1\/2, and 4) employs signals that are distinct from those that alter permeability. 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