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.
Department of Physiology, Faculty of Medicine, University of Porto, Porto, Portugal.
Tiago
T
Henriques-Coelho
Sílvia Marta
SM
Oliveira
Rute S
RS
Moura
Roberto
R
Roncon-Albuquerque
Ana Luísa
AL
Neves
Mário
M
Santos
Cristina
C
Nogueira-Silva
Filipe
F
La Fuente Carvalho
Ana
A
Brandão-Nogueira
Jorge
J
Correia-Pinto
Adelino F
AF
Leite-Moreira
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