TY - JOUR
AU - Vandenbroeck, K
AB - The metalloantibiotic bacitracin is a known inhibitor of protein disulfide isomerase (PDI). The disulfide-linked interleukin-12 (IL-12) αβ-heterodimer and β2-homodimer forms are crucial mediators of cell-mediated immune responses and inflammatory reactions. Bacitracin was found to potently block secretion of both the αβ- and β2-dimer forms of IL-12, while it did not affect secretion of the β-monomer. This inhibition coincided with a reduction in the intracellular amount of PDI found in complex with the β-chain during intracellular transit. Bacitracin did not affect mRNA levels of the α- and β-chain. Similar to bacitracin, N-acetylcysteine blocked αβ- and β2-secretion as well as PDI-β-chain complex formation. Thus, blocking PDI or shifting the endoplasmic reticulum towards a more reduced status disrupts the oxidative folding pathway or assembly of IL-12 dimer forms. The assembly stage of cytokines in the endoplasmic reticulum may represent a novel target for pharmacological intervention.
TI - The metallopeptide antibiotic bacitracin inhibits interleukin-12 αβ and β2 secretion
JF - Journal of Pharmacy and Pharmacology
DO - 10.1211/0022357055443
DA - 2005-02-01
UR - https://www.deepdyve.com/lp/oxford-university-press/the-metallopeptide-antibiotic-bacitracin-inhibits-interleukin-12-and-2-LSCZZI8v0s
SP - 213
EP - 218
VL - 57
IS - 2
DP - DeepDyve
ER -