Expression and regulation of small proline-rich protein 2 in allergic inflammation.
Asthma is a complex inflammatory pulmonary disorder that is on the rise despite intense ongoing research. We aimed to elucidate novel pathways involved in the pathogenesis of asthma. Employing asthma models induced by different allergens (ovalbumin and Aspergillus fumigatus), we uncovered the involvement of two members of the small proline-rich protein (SPRR) family, SPRR2a and SPRR2b, known to be involved in epithelial differentiation but not allergic disease. In situ hybridization revealed induction of SPRR2 signal in a subset of bronchial epithelial cells and mononuclear cells associated with inflammation after allergen challenge. Allergen-induced SPRR2 mRNA accumulation in the lung occurred in a time-dependent manner, with peak expression 10-96 h after a second ovalbumin challenge. Transgenic overexpression of interleukin (IL)-13 in the lungs resulted in a marked increase of SPRR2 expression, and allergen-induced SPRR2 expression was significantly decreased in IL-13-deficient mice. Studies in gene-targeted mice revealed that allergen-induced SPRR2 was dependent upon STAT6. Finally, we aimed to determine if the induction of SPRR2 by allergen was tissue specific. Notably, SPRR2 was markedly increased in the small intestine after induction of allergic gastrointestinal inflammation. Thus, SPRR2 is an allergen- and IL-13-induced gene in experimental allergic responses that may be involved in disease pathophysiology.
Zimmermann
Nives
N
Division of Allergy and Immunology, Cincinnati Children's Hospital Medical Center, 3333 Burnet Avenue, Cincinnati, OH 45229, USA.
Doepker
Matthew P
MP
Witte
David P
DP
Stringer
Keith F
KF
Fulkerson
Patricia C
PC
Pope
Samuel M
SM
Brandt
Eric B
EB
Mishra
Anil
A
King
Nina E
NE
Nikolaidis
Nikolaos M
NM
Wills-Karp
Marsha
M
Finkelman
Fred D
FD
Rothenberg
Marc E
ME
D000485:Allergens / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000276:immunology*; D055233:Cornified Envelope Proline-Rich Proteins; D041981:Gastrointestinal Tract / Q000276:immunology; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000378:metabolism*; D017403:In Situ Hybridization; D007249:Inflammation / Q000276:immunology*; D018793:Interleukin-13 / Q000235:genetics / Q000378:metabolism; D007381:Intermediate Filament Proteins / Q000276:immunology*; D008168:Lung / Q000276:immunology / Q000473:pathology; D008565:Membrane Proteins / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D011498:Protein Precursors / Q000276:immunology*; D050800:STAT6 Transcription Factor; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D000485:Allergens; D055233:Cornified Envelope Proline-Rich Proteins; D018793:Interleukin-13; D007381:Intermediate Filament Proteins; D008565:Membrane Proteins; D011498:Protein Precursors; D050800:STAT6 Transcription Factor; C494101:STAT6 protein, human; C491091:Sprr2a1 protein, mouse; C114978:Sprr2b protein, mouse; C494100:Stat6 protein, mouse; D015534:Trans-Activators