1.
Haem oxygenase-1 (HO-1) can exert protective effects against oxidative stress and
inflammation. Fibroblasts participate in inflammatory responses where they produce high levels of
prostaglandins (PGs) and
nitric oxide (NO). However, little is known of the presence of HO-1 in these cells and the possible interactions among these pathways. Incubation of cells with NO donors,
spermine nonoate (SPNO) and
S-nitroso-N-acetylpenicillamine (SNAP), induced a dose- and time-dependent expression of HO-1
protein. 2. NO donors increased basal
PGE(2) release although they reduced
PGE(2) accumulated in the medium and
cyclo-oxygenase (COX) activity when cells were stimulated with
lipopolysaccharide (LPS). COX-2
protein was weakly induced by SPNO in basal conditions and in the presence of LPS a synergy for HO-1 and COX-2
protein expression was observed. 3. Our results indicate that
reactive oxygen species participate in the inductive effect of NO donors or LPS on HO-1 expression, whereas endogenous NO production may play a role in the mechanism of the synergy exhibited by SPNO and LPS on HO-1 and COX-2 expression. In this system,
zinc protoporphyrin IX did not affect
nitrite levels but reduced COX activity. 4. The selective
COX-2 inhibitors SC58125 and
NS398 as well as the non-selective COX inhibitor,
indomethacin, strongly reduced
PGE(2) synthesis and showed a synergy with NO donors in HO-1 and COX-2 induction. Addition of
PGE(2) had no effect, suggesting a mechanism independent of PGs formation. 5. In inflammatory conditions a number of factors could cooperate to induce HO-1 and COX-2, with a positive regulation by COX inhibitors.