Anti-inflammatory activity of PAS-1, a protein component of Ascaris suum.
BACKGROUND
Recently, we identified a 200 kDa protein (PAS-1) from Ascaris suum worms, that suppresses the humoral immune response. Here, the effect of PAS-1 on inflammatory leukocyte migration induced by bacterial lipopolysaccharide (LPS) was investigated.


METHODS
Cellular migration and cytokine release, stimulated by LPS or LPS+PAS-1, were analyzed in air pouches induced in the shaved back of BALB/c mice. Cytokines were determined by ELISA and RT-PCR on air pouch exudates and in vitro stimulated peritoneal macrophages.


RESULTS
The significant cellular influx induced by LPS, consisting predominantly of neutrophils, was highly suppressed in the presence of PAS-1, but not a non-related protein. PAS-1 led also to a marked reduction of TNF-alpha, IL-1 beta and IL-6 levels in both LPS-stimulated air pouches and peritoneal macrophage cultures. In contrast, PAS-1 induced a significant increase of IL-10 and TGF-beta production.


CONCLUSIONS
These results demonstrate that PAS-1 has a potent anti-inflammatory activity, probably due to the stimulation of regulatory cytokines in macrophages, thus leading to the inhibition of pro-inflammatory cytokine production.
Oshiro
T M
TM
Laboratory of Immunopathology, Butantan Institute, Av. Vital Brasil 1500, 05503-900, São Paulo, SP, Brasil.
Macedo
M S
MS
Macedo-Soares
M F
MF
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000302:isolation & purification / Q000494:pharmacology*; D017165:Ascaris suum / Q000737:chemistry*; D002478:Cells, Cultured; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D005260:Female; D015801:Helminth Proteins / Q000302:isolation & purification / Q000494:pharmacology*; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects; D008070:Lipopolysaccharides / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D015801:Helminth Proteins; D008070:Lipopolysaccharides