Characterization of inflammatory reaction induced by neuwiedase, a P-I metalloproteinase isolated from Bothrops neuwiedi venom.
The Snake Venom Metalloproteinases (SVMPs) play a relevant role in the multifactorial inflammatory response induced by Bothrops envenomations. Neuwiedase, an SVMP isolated from Bothrops neuwiedi venom, is devoid of hemorrhagic activity on skin tests, but is able to induce myonecrosis and degrade fibrinogen, fibrin, type I collagen, fibronectin and laminin. In this study, we analyzed the inflammatory reaction induced by neuwiedase in gastrocnemius muscle, with special focus on cytokines release. Our results showed clear evidence of inflammatory infiltrate in the gastrocnemius muscle and an increase of MMP-9, and the cytokines KC, IL-1 beta and IL-6 in the early periods after toxin injection. The cytokine release was also evaluated in inflammatory and muscular cell culture. Both murine peritoneal adherent cells (MPACs) and muscle cells (C2C12) released pro-inflammatory cytokines after stimulus with neuwiedase. MPACs showed increased production of KC, IL-1 beta and IL-6 in the cell culture supernatant while in C2C12, the predominant chemokine expressed was KC. These data reinforce the importance of SVMPs in the inflammatory response caused by envenomation and point out the role of muscle cells in this event by releasing pro-inflammatory mediators able to attract leukocytes to the muscle, thus starting and amplifying the setting of the inflammatory reaction.
Lopes
Daiana Silva
DS
Laboratório de Imunopatologia, Instituto Butantan, Av. Dr. Vital Brasil 1500, 05503-900 São Paulo, SP, Brazil.
Baldo
Cristiani
C
Oliveira
Carolina de Freitas
Cde F
de Alcântara
Tânia Machado
TM
Oliveira
Jaqueline D Dias
JD
Gourlart
Luiz Ricardo
LR
Hamaguchi
Amélia
A
Homsi-Brandeburgo
Maria Inês
MI
Moura-da-Silva
Ana Maria
AM
Clissa
Patricia Bianca
PB
Rodrigues
Veridiana de Melo
Vde M
D000818:Animals; D017837:Bothrops / Q000502:physiology*; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D007249:Inflammation / Q000139:chemically induced* / Q000473:pathology; D008666:Metalloendopeptidases / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014757:Viper Venoms / Q000633:toxicity*
D018925:Chemokines; D016207:Cytokines; D014757:Viper Venoms; D008666:Metalloendopeptidases; C414740:neuwiedase