title: Cytokine profiling identifies an interaction of IL-6 and IL-1α to drive PSMA-PSA prostate clones.
abstract: Several PSMA-PSA prostate clones have been identified during prostate cancer progression; however, until now, their in situ inflammatory characteristics have remained unclear.
  
  
  
  We therefore investigated the interplay between proinflammatory cytokines and (PSMA,PSA) sub-groups.
  
  
  
  27 benign prostate hyperplasia (BPH) and 18 prostate cancers (PC) were enrolled in this study. Immunohistochemical analysis was performed. Serum levels of PSA were assayed by Immulite autoanalyser.
  
  
  
  In BPH and PC patients with elevated serum PSA levels, IL-1α was the most proinflammatory cytokine expressed in (PSMA+,PSA-) subgroup. However, most samples of (PSMA+,PSA+) subgroup had positive immunoreaction to IL-6. In samples of PC with PSA serum levels of 4-20ng/mL or >20ng/mL, immunoreaction to TNF-α was seen only in (PSMA+,PSA+) subgroup. Interestingly, several combinations of proinflammatory cytokines (IL-6, IL-1α and TNF-α) showed that coexpression of tissue PSMA and PSA was concomitant with high immunoreactions to (IL-6+,TNF-α-), (IL-6+,IL-1α+) and (IL-1α+,TNFα-) in BPH and PC patients. (PSMA,PSA) subgroup lacking tissue PSA expression showed a high immunoexpression of the profile (IL-6+,TNF-α-). The combinations of (IL-6-, TNF-α-) and (IL-6-, IL-1α-) were absent in (PSMA+,PSA-) and (PSMA+,PSA+) BPH sub-groups.
  
  
  
  Collectively, these findings underscore the importance of TNF-α and highlight the interaction between IL-6 and IL-1α to generate an inflammatory microenvironment in driving (PSMA,PSA) prostate clones.
authors.affiliation: Unit of Immunology and Microbiology Environmental and Carcinogenesis (IMEC), Faculty of Sciences of Bizerte, 7021, Zarzouna, University of Carthage, Tunisia.
authors.forename: Awatef Ben
authors.initials: AB
authors.lastname: Jemaa
authors.affiliation: Unit of Immunology and Microbiology Environmental and Carcinogenesis (IMEC), Faculty of Sciences of Bizerte, 7021, Zarzouna, University of Carthage, Tunisia.
authors.forename: Yosra
authors.initials: Y
authors.lastname: Bouraoui
authors.affiliation: Department of Urology, Hospital of Military Tunis, Tunisia.
authors.forename: Nawfel Ben
authors.initials: NB
authors.lastname: Rais
authors.affiliation: Department of Urology, Hospital of La Rabta Tunis, Tunisia.
authors.forename: Yassine
authors.initials: Y
authors.lastname: Nouira
authors.affiliation: Unit of Immunology and Microbiology Environmental and Carcinogenesis (IMEC), Faculty of Sciences of Bizerte, 7021, Zarzouna, University of Carthage, Tunisia. Electronic address: oueslatiridha12@hotmail.fr.
authors.forename: Ridha
authors.initials: R
authors.lastname: Oueslati
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000954:Antigens, Surface / Q000378:metabolism; D063646:Carcinogenesis; D002999:Clone Cells; D004847:Epithelial Cells / Q000378:metabolism* / Q000473:pathology; D020869:Gene Expression Profiling; D043425:Glutamate Carboxypeptidase II / Q000378:metabolism; D006801:Humans; D053582:Interleukin-1alpha / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000276:immunology* / Q000473:pathology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000276:immunology*; D011471:Prostatic Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D000954:Antigens, Surface; D053582:Interleukin-1alpha; D015850:Interleukin-6; C473848:FOLH1 protein, human; D043425:Glutamate Carboxypeptidase II; D017430:Prostate-Specific Antigen
keywords: Benign prostate hyperplasia; IL-1α; IL-6; PSA; PSMA; Prostate cancer; TNFα