Thymulin inhibits monocrotaline-induced pulmonary hypertension modulating interleukin-6 expression and suppressing p38 pathway.
The pathogenesis of pulmonary hypertension (PH) includes an inflammatory response. Thymulin, a zinc-dependent thymic hormone, has important immunobiological effects by inhibiting various proinflammatory cytokines and chemokines. We investigated morphological and hemodynamic effects of thymulin administration in a rat model of monocrotaline (MCT)-induced PH, as well as the pattern of proinflammatory cytokine gene expression and the intracellular pathways involved. Adult Wistar rats received an injection of MCT (60 mg/kg, sc) or an equal volume of saline. One day after, the animals randomly received during 3 wk an injection of saline, vehicle (zinc plus carboxymethyl cellulose), or thymulin (100 ng/kg, sc, daily). At d 23-25, the animals were anesthetized for hemodynamic recordings, whereas heart and lungs were collected for morphometric and molecular analysis. Thymulin prevented morphological, hemodynamic, and inflammatory cardiopulmonary profile characteristic of MCT-induced PH, whereas part of these effects were also observed in MCT-treated animals injected with the thymulin's vehicle containing zinc. The pulmonary thymulin effect was likely mediated through suppression of p38 pathway.
Henriques-Coelho
Tiago
T
Department of Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
Oliveira
Sílvia Marta
SM
Moura
Rute S
RS
Roncon-Albuquerque
Roberto
R
Neves
Ana Luísa
AL
Santos
Mário
M
Nogueira-Silva
Cristina
C
La Fuente Carvalho
Filipe
F
Brandão-Nogueira
Ana
A
Correia-Pinto
Jorge
J
Leite-Moreira
Adelino F
AF
D000818:Animals; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000139:chemically induced* / Q000235:genetics / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D008168:Lung / Q000033:anatomy & histology / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects* / Q000235:genetics; D008297:Male; D016686:Monocrotaline; D051381:Rats; D017208:Rats, Wistar; D013935:Thymic Factor, Circulating / Q000494:pharmacology* / Q000627:therapeutic use; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism / Q000502:physiology
D016207:Cytokines; D018836:Inflammation Mediators; D015850:Interleukin-6; D016686:Monocrotaline; D013935:Thymic Factor, Circulating; D048051:p38 Mitogen-Activated Protein Kinases