INVESTIGADORES
PITOSSI Fernando Juan
artículos
Título:
Transient expression of IL-1â induces
Autor/es:
MARTIN KOLB; PETER J. MARGETTS; DANIEL C. ANTHONY; FERNANDO PITOSSI
Revista:
JOURNAL OF CLINICAL INVESTIGATION
Editorial:
AMER SOC CLINICAL INVESTIGATION INC
Referencias:
Lugar: Ann Arbor, Michigan; Año: 2001 vol. 107 p. 1529 - 1536
ISSN:
0021-9738
Resumen:
IL-1â is one of a family of proinflammatory cytokines thought to be involved in many acute and chronic
diseases. Although it is considered to participate in wound repair, no major role has been attributed to
IL-1â in tissue fibrosis. We used adenoviral gene transfer to transiently overexpress IL-1â in rat lungs after
intratracheal administration. The high expression of IL-1â in the first week after injection was accompanied
by local increase of the proinflammatory cytokines IL-6 and TNF-á and a vigorous acute inflammatory
tissue response with evidence of tissue injury. The profibrotic cytokines PDGF and TGF-â1 were
increased in lung fluid samples 1 week after peak expression of IL-1â. Although PDGF returned to baseline
in the third week, TGF-â1 showed increased concentrations in bronchoalveolar lavage fluid for up to
60 days. This was associated with severe progressive tissue fibrosis in the lung, as shown by the presence
of myofibroblasts, fibroblast foci, and significant extracellular accumulations of collagen and fibronectin.
These data directly demonstrate how acute tissue injury in the lung, initiated by a highly proinflammatory
cytokine, IL-1â, converts to progressive fibrotic changes. IL-1â should be considered a valid target for
therapeutic intervention in diseases associated with fibrosis and tissue remodeling