title: Creatine activates airway epithelium in asthma.
abstract: Airway epithelium plays important roles in the pathophysiology of asthma. Creatine supplementation (Cr) was shown to increase asthma features in a murine model of allergic asthma; however, the role of the airway epithelium in this inflammatory response is not known. BALB/c mice were divided into control, creatine supplementation, ovalbumin-sensitized (OVA) and OVA plus creatine supplementation groups. OVA sensitization occurred on days 0, 14, 28 and 42, and ovalbumin challenge from days 21-53. Cr was also given on days 21-53. Total and differential cells counts in BALF were evaluated. Quantitative epithelial expression of interleukin (IL)-4, IL-5, IL-13, CCL11, CCL5, CCL2, iNOS, VCAM-1, ICAM-1, NF-κB, VEGF, TGF-β, IGF-1, EGFR, TIMP-1, TIMP-2, MMP-9, MMP-12 and arginase II were performed. Cr increased the number of total cells and eosinophils in BALF, the epithelial content of goblet cells and the epithelial expression of IL-5, CCL2, iNOS, ICAM-1, NF-κB, TGF-β, TIMP-1 and MMP-9 when compared to the control group (p<0.05). Creatine supplementation also exacerbated goblet cell proliferation, and IL-5 and iNOS expression by epithelial cells compared to the OVA group (p<0.01). Creatine up-regulates the pro-inflammatory cascade and remodelling process in this asthma model by modulating the expression of inflammatory mediators by epithelial cells.
authors.affiliation: University of Sao Paulo, Pathology (LIM 05), Sao Paulo, Brazil.
authors.forename: S C
authors.initials: SC
authors.lastname: Ferreira
authors.forename: A C
authors.initials: AC
authors.lastname: Toledo
authors.forename: M
authors.initials: M
authors.lastname: Hage
authors.forename: A B G
authors.initials: AB
authors.lastname: Santos
authors.forename: M C R
authors.initials: MC
authors.lastname: Medeiros
authors.forename: M A
authors.initials: MA
authors.lastname: Martins
authors.forename: C R F
authors.initials: CR
authors.lastname: Carvalho
authors.forename: M
authors.initials: M
authors.lastname: Dolhnikoff
authors.forename: R P
authors.initials: RP
authors.lastname: Vieira
mesh_terms: D000818:Animals; D001249:Asthma / Q000209:etiology* / Q000503:physiopathology; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D049109:Cell Proliferation / Q000187:drug effects; D003401:Creatine / Q000633:toxicity*; D004195:Disease Models, Animal; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D020397:Goblet Cells / Q000187:drug effects; D018836:Inflammation Mediators / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin; D013997:Time Factors
chemical_list: D018836:Inflammation Mediators; D010047:Ovalbumin; D003401:Creatine