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

Research output: Contribution to journalArticle

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-1β). ECV304 cells transfected with HLA-B*3501 and HLA-B*0801 polymorphic α chain or with pIRESneo2 were incubated with 100 U/ml of IL-1β 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.

Original languageEnglish
Pages (from-to)239-244
Number of pages6
JournalTissue Antigens
Volume68
Issue number3
DOIs
Publication statusPublished - Sep 2006

Keywords

  • ECV304
  • Endothelin-1
  • HLA class I
  • HLA-B35
  • Interleukin-1β
  • Pulmonary hypertension
  • Systemic sclerosis

ASJC Scopus subject areas

  • Cell Biology
  • Immunology

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