title: TSLP induces mast cell development and aggravates allergic reactions through the activation of MDM2 and STAT6.
abstract: Thymic stromal lymphopoietin (TSLP) is known to promote T helper type 2 cell-associated inflammation. Mast cells are major effector cells in allergic inflammatory responses. We noted that the population and maturation of mast cells were reduced in TSLP-deficient mice (TSLP-/-). Thus, we hypothesized that TSLP might affect mast cell development. We found that TSLP induced the proliferation and differentiation of mast cells from bone marrow progenitors. TSLP-induced mast cell proliferation was abolished by depletion of mouse double minute 2 (MDM2) and signal transducers and activators of transcription 6 (STAT6), as an upstream activator of MDM2. TSLP-/-, in particular, had a considerable deficit in the expression of MDM2 and STAT6. Also, the TSLP deficiency attenuated mast cell-mediated allergic reactions through the downregulation of STAT6 and MDM2. In an antibody microarray chip analysis, MDM2 expression was increased in atopic dermatitis patients. These observations indicate that TSLP is a factor for mast cell development, and that it aggravates mast cell-mediated immune responses.
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Na-Ra
authors.initials: NR
authors.lastname: Han
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Hyun-A
authors.initials: HA
authors.lastname: Oh
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea.
authors.forename: Sun-Young
authors.initials: SY
authors.lastname: Nam
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea. Electronic address: pdmoon@khu.ac.kr.
authors.forename: Phil-Dong
authors.initials: PD
authors.lastname: Moon
authors.affiliation: Department of Dermatology, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Do-Won
authors.initials: DW
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, College of Korean Medicine, Kyung Hee University, Dongdaemun-gu, Seoul, Republic of Korea. Electronic address: hmkim@khu.ac.kr.
authors.forename: Hyung-Min
authors.initials: HM
authors.lastname: Kim
authors.affiliation: Inflammatory Disease Research Center and Biochip Research Center, Hoseo University, Asan, Chungnam, Republic of Korea. Electronic address: hjjeong@hoseo.edu.
authors.forename: Hyun-Ja
authors.initials: HJ
authors.lastname: Jeong
mesh_terms: D000818:Animals; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D016207:Cytokines / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D003876:Dermatitis, Atopic / Q000503:physiopathology*; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology; D005260:Female; D006967:Hypersensitivity / Q000503:physiopathology; D008407:Mast Cells / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D051736:Proto-Oncogene Proteins c-mdm2 / Q000502:physiology*; D050800:STAT6 Transcription Factor / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology; D000094632:Thymic Stromal Lymphopoietin
chemical_list: D016207:Cytokines; D050800:STAT6 Transcription Factor; C494100:Stat6 protein, mouse; C497207:Mdm2 protein, mouse; D051736:Proto-Oncogene Proteins c-mdm2; D000094632:Thymic Stromal Lymphopoietin; C000721967:TSLP protein, mouse
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