HLA-B35 upregulates the production of endothelin-1 in HLA-transfected cells: a possible pathogenetic role in pulmonary hypertension.
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| Abstract |
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-1beta). 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-1beta 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.
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| Authors | A Santaniello, G Salazar, S Lenna, R Antonioli, G Colombo, L Beretta, R Scorza |
| Journal | Tissue antigens (Tissue Antigens) Vol. 68 Issue 3 Pg. 239-44 (Sep 2006) ISSN: 0001-2815 [Print] England |
| PMID | 16948645 (Publication Type: Journal Article) |
| Chemical References |
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