title: Podocytes are the major source of IL-1 alpha and IL-1 beta in human glomerulonephritides.
abstract: To address the question of in situ production of IL-1 alpha and IL-1 beta in proliferative and non-proliferative forms of human glomerulonephritis (GN), we performed immunocytochemical and in situ hybridization studies on renal biopsies from patients with mesangial IgA-GN (N = 38), idiopathic membranous GN (MGN; N = 12), minimal change disease (MCD; N = 9), focal segmental glomerulosclerosis (FSGS; N = 5) and acute endocapillary GN (AGN; N = 3). Normal kidneys (N = 10) served as controls. Concomitantly, the expression of IL-1 receptor type I (IL-1 RI), IL-1 receptor type II (IL-1 RII) and of IL-1 receptor antagonist (IL-1 RA) was analyzed. Antibodies against antigens expressed on podocytes (PP-44), endothelial cells (CD31) and monocytes/macrophages (CD11b, CD14, CD68) were applied to attribute the expression of IL-1/IL-1 related peptides to intrinsic glomerular and/or blood-derived infiltrating cells. Our results demonstrate that IL-1 RII is constitutively expressed on endothelial cells, and its expression can be induced in proximal tubular cells and in the interstitium. In diseased glomeruli podocytes are capable of producing IL-1 alpha/beta. In MGN and MCD/FSGS, the expression of both IL-1 forms is particularly noted in early stages of the disease and is not only accompanied by a marked reactivity for IL-1 RI, but also for IL-1 RA. In segmental sclerosing lesions in FSGS and in IgA-GN with marked glomerular proliferation and/or sclerosis, a reduced expression of the PP-44 antigen and a diminished ability of podocytes to produce IL-1/IL-1 related peptides are noted. These results suggest that intrinsic glomerular production of IL-1 may be of relevance for the protection of glomeruli from continuing injury.
authors.affiliation: Department of Pathology, Ruperto-Carola University, Heidelberg, Germany.
authors.forename: Z I
authors.initials: ZI
authors.lastname: Niemir
authors.forename: H
authors.initials: H
authors.lastname: Stein
authors.forename: G
authors.initials: G
authors.lastname: Dworacki
authors.forename: P
authors.initials: P
authors.lastname: Mundel
authors.forename: N
authors.initials: N
authors.lastname: Koehl
authors.forename: B
authors.initials: B
authors.lastname: Koch
authors.forename: F
authors.initials: F
authors.lastname: Autschbach
authors.forename: K
authors.initials: K
authors.lastname: Andrassy
authors.forename: E
authors.initials: E
authors.lastname: Ritz
authors.forename: R
authors.initials: R
authors.lastname: Waldherr
authors.forename: H F
authors.initials: HF
authors.lastname: Otto
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002196:Capillaries / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D005260:Female; D005922:Glomerulonephritis, IGA / Q000378:metabolism* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D007668:Kidney / Q000098:blood supply / Q000473:pathology; D007678:Kidney Glomerulus / Q000737:chemistry / Q000166:cytology / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009402:Nephrosis, Lipoid / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D007375:Interleukin-1; D012333:RNA, Messenger