title: Augmented pulmonary IL-4 and IL-13 receptor subunit expression in idiopathic interstitial pneumonia.
abstract: BACKGROUND
  Some idiopathic interstitial pneumonias (IIPs) are characterised by fibroproliferation and deposition of extracellular matrix. Because efficacious treatment options are limited, research has been directed towards understanding the cytokine networks that may affect fibroblast activation and, hence, the progression of certain IIPs.
  
  
  OBJECTIVE
  To examine the expression of interleukin 4 (IL-4), IL-13, and their corresponding receptor subunits in the various forms of IIP and normal patient groups.
  
  
  METHODS
  Molecular and immunohistochemical analysis of IL-4, interferon gamma (IFNgamma), IL-13, IL-4 receptor (IL-R), and IL-13 receptor subunits in surgical lung biopsies (SLBs) from 39 patients (21 usual interstitial pneumonia (UIP), six non-specific interstitial pneumonia (NSIP), eight respiratory bronchiolitic interstitial lung disease (RBILD), and five normal controls).
  
  
  RESULTS
  Molecular analysis demonstrated that IL-13Ralpha2, IL-13Ralpha1, and IL-4Ralpha were present in a greater proportion of upper and lower lobe biopsies from patients with UIP than patients with NSIP and RBILD. Immunohistochemical analysis of patients with UIP, NSIP, and RBILD revealed interstitial staining for all three receptor subunits, whereas such staining was only seen in mononuclear cells present in normal SLBs. Fibroblastic foci in patients with UIP strongly stained for IL-4Ralpha and IL-13Ralpha2. Localised expression of IL-4Ralpha was also seen in SLBs from patients with NSIP but not in other groups.
  
  
  CONCLUSIONS
  Some histological subtypes of IIP are associated with increased pulmonary expression of receptor subunits responsive to IL-4 and IL-13. These findings may be of particular importance in understanding the pathogenesis of IIP and, more importantly, may provide important novel therapeutic targets.
authors.affiliation: Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0602, USA.
authors.forename: C
authors.initials: C
authors.lastname: Jakubzick
authors.forename: E S
authors.initials: ES
authors.lastname: Choi
authors.forename: S L
authors.initials: SL
authors.lastname: Kunkel
authors.forename: H
authors.initials: H
authors.lastname: Evanoff
authors.forename: F J
authors.initials: FJ
authors.lastname: Martinez
authors.forename: R K
authors.initials: RK
authors.lastname: Puri
authors.forename: K R
authors.initials: KR
authors.lastname: Flaherty
authors.forename: G B
authors.initials: GB
authors.lastname: Toews
authors.forename: T V
authors.initials: TV
authors.lastname: Colby
authors.forename: E A
authors.initials: EA
authors.lastname: Kazerooni
authors.forename: B H
authors.initials: BH
authors.lastname: Gross
authors.forename: W D
authors.initials: WD
authors.lastname: Travis
authors.forename: C M
authors.initials: CM
authors.lastname: Hogaboam
mesh_terms: D000328:Adult; D000368:Aged; D001706:Biopsy; D005260:Female; D015870:Gene Expression; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D053661:Interleukin-13 Receptor alpha1 Subunit; D015847:Interleukin-4 / Q000235:genetics / Q000378:metabolism; D008168:Lung / Q000378:metabolism*; D017563:Lung Diseases, Interstitial / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D018123:Receptors, Interleukin / Q000235:genetics / Q000378:metabolism*; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4 / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: C508181:IL13RA1 protein, human; D018793:Interleukin-13; D053661:Interleukin-13 Receptor alpha1 Subunit; D012333:RNA, Messenger; D018123:Receptors, Interleukin; D053660:Receptors, Interleukin-13; D019948:Receptors, Interleukin-4; D015847:Interleukin-4; D007371:Interferon-gamma