IFN-gamma stimulates the expression of a novel secretoglobin that regulates chemotactic cell migration and invasion.
IFNs are a family of cytokines that alert the immune system against viral infections of host cells. The IFNs (IFN-alpha, IFN-beta, and IFN-gamma) interact with specific cellular receptors and stimulate the production of second messengers, leading to the expression of antiviral and immunomodulatory proteins. We report in this study that IFN-gamma stimulates the expression of a novel gene that encodes a protein with 30% amino acid sequence identity with uteroglobin, the founding member of the newly formed Secretoglobin (SCGB) superfamily. We named this protein IFN-gamma-inducible SCGB (IIS), because its expression in lymphoblast cells is augmented by IFN-gamma treatment. IIS is expressed in virtually all tissues, and the highest level of expression is detectable in lymph nodes, tonsil, cultured lymphoblasts, and the ovary. Interestingly, although the expression of IIS mRNA is not significantly different in resting lymphoid cells, it is markedly elevated in activated CD8(+) and CD19(+) cells. Furthermore, treatment of lymphoblast cells with IIS antisense phosphorothioate (S)-oligonucleotides prevents chemotactic migration and invasion. Taken together, these results raise the possibility that this novel SCGB has immunological functions.
Choi
Moonsuk S
MS
Section on Developmental Genetics, Heritable Disorders Branch, National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD 20892, USA.
Ray
Rabindranath
R
Zhang
Zhongjian
Z
Mukherjee
Anil B
AB
D000595:Amino Acid Sequence; D000818:Animals; D018941:Antigens, CD19 / Q000096:biosynthesis; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D019556:COS Cells; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D002464:Cell Migration Inhibition; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D005786:Gene Expression Regulation / Q000276:immunology; D006801:Humans; D007371:Interferon-gamma / Q000502:physiology*; D007399:Interphase / Q000235:genetics / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008969:Molecular Sequence Data; D005810:Multigene Family / Q000276:immunology*; D009185:Myelin Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D041681:NIH 3T3 Cells; D009928:Organ Specificity / Q000235:genetics / Q000276:immunology; D011110:Polymorphism, Genetic / Q000276:immunology; D011510:Proteolipids / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology*; D012333:RNA, Messenger / Q000096:biosynthesis; D060765:Secretoglobins; D014598:Uteroglobin
D018941:Antigens, CD19; D009185:Myelin Proteins; D011510:Proteolipids; D012333:RNA, Messenger; C556466:SCGB1D4 protein, human; D060765:Secretoglobins; D007371:Interferon-gamma; D014598:Uteroglobin