Uteroglobin suppresses allergen-induced TH2 differentiation by down-regulating the expression of serum amyloid A and SOCS-3 genes.
Allergen-induced airway inflammation may lead to allergic asthma, a chronic inflammatory disease of the respiratory system. Despite its high incidence, the majority of the world's population is unaffected by allergic airway inflammation most likely due to innate protective mechanism(s) in the respiratory system. The mammalian airway epithelia constitutively express uteroglobin (UG), a protein with potent anti-inflammatory and anti-chemotactic properties. We report here that UG binds to FPR2, a G-protein coupled receptor, inhibits chemotaxis, down-regulates SOCS-3 gene expression and STAT-1 activation, which are critical for the differentiation of T-helper 2 (T(H)2) cells that secrete pro-inflammatory T(H)2 cytokines. We propose that UG suppresses allergen-mediated activation of T(H)2 response by down-regulating the expression of genes that are critical for T(H)2 differentiation.
Ray
Rabindranath
R
Section on Developmental Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, The National Institutes of Health, Building 10, Rm 9D42, 10, Center Drive, Bethesda, MD 20892-1830, USA.
Zhang
Zhongjian
Z
Lee
Yi-Ching
YC
Gao
Ji-Liang
JL
Mukherjee
Anil B
AB
D000485:Allergens / Q000008:administration & dosage; D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation; D002645:Chickens; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation; D008168:Lung / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D044042:Receptors, Formyl Peptide / Q000235:genetics; D050794:STAT1 Transcription Factor / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000235:genetics*; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics*; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology*; D014598:Uteroglobin / Q000172:deficiency / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
D000485:Allergens; D017931:DNA Primers; D044042:Receptors, Formyl Peptide; D050794:STAT1 Transcription Factor; D000685:Serum Amyloid A Protein; C491411:Socs3 protein, mouse; C494080:Stat1 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; C481578:formyl peptide receptor 2, mouse; D010047:Ovalbumin; D014598:Uteroglobin