HLA-B35 is associated with an increased risk for developing isolated pulmonary hypertension (iPHT) in systemic sclerosis, but the mechanisms underlying this association have not been fully elucidated yet. Endothelin-1 (ET-1) is the main pathogenetic molecule implied in the development of iPHT; therefore, we sought to determine if ECV304 cells transfected with the HLA-B35 allele produce increased amounts of ET-1 after incubation with physiological concentrations of interleukin-1 beta (IL-1(beta)). ECV304 cells transfected with HLA-B*3501 and HLA-B*0801 polymorphic (alpha) chain or with pIRESneo2 were incubated with 100 U/ml of IL-1(beta) for 6, 12, 24, 36 and 48 h. ET-1 levels were determined using EIA kit (CAYMAN Chemical, Ann Arbor, MI) in supernatants from different cell cultures; the relative expression of the preproendothelin-1 (PPET-1) gene was also determined by reverse transcription-polymerase chain reaction. Cells expressing the HLA-B35 allele showed significantly increased levels of ET-1 at all the selected times compared with controls or HLA-B8-transfected cells. The relative expression of the PPET-1 gene was also increased in a proportionally direct manner. The HLA-B35 allele influences the production of ET-1 in HLA-B35-transfected ECV304 cells by promoting the expression of its precursor, PPET-1. Our results provide an explanation for the epidemiological association existing between iPHT and HLA-B35. (copyright) 2006 The Authors.
HLA-B35 upregulates the production of endothelin-1 in HLA-transfected cells : a possible pathogenetic role in pulmonary hypertension / A. Santaniello, G. Salazar, S. Lenna, R. Antonioli, G. Colombo, L. Beretta, R. Scorza. - In: TISSUE ANTIGENS. - ISSN 0001-2815. - 68:3(2006 Sep), pp. 239-244.
|Titolo:||HLA-B35 upregulates the production of endothelin-1 in HLA-transfected cells : a possible pathogenetic role in pulmonary hypertension|
SANTANIELLO, ALESSANDRO (Primo)
SCORZA, RAFFAELLA (Ultimo)
|Parole Chiave:||HLA-B35 ; Endothelin-1 ; pulmonary hypertention|
|Settore Scientifico Disciplinare:||Settore MED/09 - Medicina Interna|
|Data di pubblicazione:||set-2006|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1111/j.1399-0039.2006.00657.x|
|Appare nelle tipologie:||01 - Articolo su periodico|