1: Free Radic Res. 2004 Jul;38(7):675-82. 

alpha-lipoic acid inhibits endotoxin-stimulated expression of iNOS and nitric
oxide independent of the heat shock response in RAW 264.7 cells.

Demarco VG, Scumpia PO, Bosanquet JP, Skimming JW.

Department of Child Health, University of Missouri, Columbia, MO 65211, USA.

The heat shock response protects against sepsis-induced mortality, organ injury,
cardiovascular dysfunction, and apoptosis. Several inducers of the heat shock
response, such as hyperthermia, sodium arsenite, and pyrollidine
dithiocarbonate, inhibit NF-kappaB activation and nitric oxide formation. The
antioxidant lipoic acid (LA) has recently been found to inhibit NF-kappaB
activation and nitric oxide formation. We therefore tested the hypothesis that
LA induces a heat shock response. To test this hypothesis, we determined whether
exposure to LA affects expression of both heat shock protein 70 (HSP-70) and
nuclear heat shock factor-1 (HSF-1) in lipopolysaccharide (LPS) stimulated
macrophages. LA and hyperthermia attenuated LPS-induced increases in nuclear
NF-kappaB, iNOS protein, and media nitrite concentrations. LPS and hyperthermia
increased HSP-70 concentrations 8-fold and 20-fold, respectively. No effect of
LA treatment alone on HSP-70 protein expression was detected. Likewise, no
effect of LA on HSF-1 protein expression was detected. These data suggest that
LA inhibits LPS-induced activation of iNOS in macrophages independent of the
heat shock response.

PMID: 15453632 [PubMed - indexed for MEDLINE]


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2: FEBS Lett. 2001 Nov 9;508(1):61-6. 

Role of cyclopentenone prostaglandins in rat carrageenin pleurisy.

Ianaro A, Ialenti A, Maffia P, Pisano B, Di Rosa M.

Department of Experimental Pharmacology, University of Naples Federico II, Via
Domenico Montesano 49, 80131 Naples, Italy. ianaro@unina.it

In this study, using rat carrageenin-induced pleurisy, we found that treatment
of rats with either indomethacin or NS-398 suppressed the pleurisy at 2 h but
significantly exacerbated this reaction at 48 h. Exacerbated inflammation was
associated with reduced prostaglandin D(2) levels, decreased heat shock factor 1
(HSF1) activation, reduced hsp72 expression and increased activation of nuclear
factor kappaB (NF-kappaB). Replacement of cyclopentenone prostaglandins by
treating rats with either prostaglandin J(2) or prostaglandin D(2) reversed the
exacerbating effects of cyclooxygenase inhibitors leading to the resolution of
the reaction. In conclusion, we demonstrate that cyclopentenone prostaglandins
may act as anti-inflammatory mediators by inducing in inflammatory cells
HSF1-dependent hsp72 expression and NF-kappaB inhibition, two crucial events for
the remission of inflammation.

PMID: 11707269 [PubMed - indexed for MEDLINE]


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