title: Low-molecular-weight heparin and unfractionated heparin decrease Th-1, 2, and 17 expressions.
abstract: BACKGROUND
  We evaluated the effects of T helper cell differentiation in a mite-allergic animal model treated with inhaled heparins of different molecular weight.
  
  
  METHODS
  BALB/c mice were divided into four groups: 1. Control, 2. Mite intratracheal (mIT), 3. Inhaled heparin (hIN), 4. Inhaled low-molecular-weight heparin (lmwhIN). Groups 2, 3, and 4 were sensitized twice with Der p allergen subcutaneously on day 1 and day 8. Der p allergen was administered intratracheally on day 15. Groups 3 and 4 were treated with heparin or low-molecular-weight (lmw) heparin intranasally from day 1 to 22. Splenocytes from sacrificed mice stimulated with 16 µg/ml of Der p were cultured for 72 hours. Supernatants of splenocyte were collected to analyze the effect of Interleukin (IL)17-A/F, Interferon(IFN)-γ, IL-4, IL-13, and IL-10. Serum was also collected for Der P-specific IgE level on day 23. Total RNA was extracted from spleen tissue for mRNA expression. Gene expression of Foxp3, IL-10 IFN-γ, GATA3, IL-5, and RORγt were analyzed.
  
  
  RESULTS
  Both hIN and lmwhIN groups had lower serum IgE level than that of the mIT group (both p<0.0001). Both hIN and lmwhIN groups showed significantly decreased transcripts of GATA-3, IFN-γ, IL-5, and RORγt mRNA in their spleen. Regarding the supernatant of splenocyte culture stimulated with Der p, compared with the mIT group, there were significant decreases in IL-17A/F, IFN-γ, IL-4, IL-13, and IL-10 secretion in inhaled hIN and lmwhIN groups.
  
  
  CONCLUSIONS
  From this balb/c mice study, the analyses of mRNA and cytokines revealed that both intranasal heparin and lmw heparin treatment decreased the expression of Th1, Th2, and Th17 in spleen. The underlying mechanism(s) warrant further studies.
authors.affiliation: Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Jing-Ning
authors.initials: JN
authors.lastname: Huang
authors.affiliation: Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Ming-Chin
authors.initials: MC
authors.lastname: Tsai
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Shun-Lung
authors.initials: SL
authors.lastname: Fang
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Margaret Dah-Tsyr
authors.initials: MD
authors.lastname: Chang
authors.affiliation: Institute of Molecular and Cellular Biology, National Tsing Hua University, Hsinchu, Taiwan, Republic of China; Department of Medical Science, National Tsing Hua University, Hsinchu, Taiwan, Republic of China.
authors.forename: Yu-Rou
authors.initials: YR
authors.lastname: Wu
authors.affiliation: Medical Research, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Jaw-Ji
authors.initials: JJ
authors.lastname: Tsai
authors.affiliation: Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China; Department of Pediatrics, National Yang-Ming Medical University, Taipei, Taiwan, Republic of China.
authors.forename: Lin-Shien
authors.initials: LS
authors.lastname: Fu
authors.affiliation: Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Heng-Kuei
authors.initials: HK
authors.lastname: Lin
authors.affiliation: Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Yi-Jun
authors.initials: YJ
authors.lastname: Chen
authors.affiliation: Pediatric Department, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China.
authors.forename: Tsai-Wei
authors.initials: TW
authors.lastname: Li
mesh_terms: D000818:Animals; D000918:Antibody Specificity / Q000276:immunology; D039741:Antigens, Dermatophagoides / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis; D005786:Gene Expression Regulation / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology*; D007073:Immunoglobulin E / Q000097:blood / Q000276:immunology; D020381:Interleukin-17 / Q000096:biosynthesis* / Q000235:genetics; D008297:Male; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000276:immunology; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*; D018418:Th2 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism*
chemical_list: D039741:Antigens, Dermatophagoides; D016207:Cytokines; D006495:Heparin, Low-Molecular-Weight; D020381:Interleukin-17; D012333:RNA, Messenger; D007073:Immunoglobulin E; D006493:Heparin