Abstract:Objective To investigate the effects of 1,25-(OH)2D3 on the airway remodeling and expression of high-mobility group box 1 (HMGB1) and Toll-like receptor 4 (TLR4) in the lungs among asthmatic mice. Methods Thirty female mice (BALB/c strain) were randomly divided into control, asthma and 1,25-(OH)2D3 intervention groups. An asthmatic mouse model was established by intraperitoneal injection and aerosol inhalation of ovalbumin. The intervention group was given 1,25-(OH)2D3 by intraperitoneal injection 0.5 hour before each aerosol inhalation, while the control group used normal saline instead. The hematoxylin-eosin staining was used to observe the mouse airway structural changes. The mRNA and protein expression of HMGB1 and TLR4 was measured by RT-PCR and immunohistochemistry, respectively. Pearson correlation analysis was performed. Results The asthma group had a significantly increased airway wall thickness compared with the control group (P<0.05); the intervention group had a significantly lower increase in airway wall thickness than the asthma group (P<0.05). The mRNA and protein expression of HMGB1 and TLR4 was significantly higher in the asthma group than in the control group (P<0.05); the mRNA and protein expression of HMGB1 and TLR4 in the intervention group was significantly lower than that in the asthma group, but still higher than that in the control group (P<0.05). A positive correlation was found between the protein expression of HMGB1 and TLR4 (P<0.01), and so was their mRNA expression (P<0.01). Conclusions HMGB1 and TLR4 may be involved in asthmatic airway remodeling. 1,25-(OH)2D3 can reduce the airway remodeling in asthmatic mice, which may be related to the downregulation of HMGB1 and TLR4 expression in the lungs of asthmatic mice.
GU Hui-Ru,LUAN Bin,QIAO Jun-Ying et al. Effect of 1,25-(OH)2D3 on expression of HMGB1 and TLR4 in the lungs of asthmatic mice[J]. CJCP, 2014, 16(3): 301-305.
Scaffidi P, Misteli T, Bianchi ME. Release of chromatin protein HMGB1 by necrotic cells triggers inflammation[J]. Nature, 2002, 418(6894): 191-195.
[7]
Messmer D, Yang H, Telusma G, et al. High mobility group box 1 (HMGB1) is an endogenous Th1 polarizing signal fordendritic cellmaturation[J]. J Immunol, 2004, 173(1): 307-313.
[8]
Dumitriu IE, Bianchi ME, Bacci M, et al. The secretion of HMGB1 is required for the migration of maturing dendritic cells[J]. J Leukoc Biol, 2007, 81(1): 84-91.
[9]
Crespo-Lessmann A, Juarez-Rubio C, Plaza-Moral V. Role of Toll like receptors in respiratory diseases[J]. Arch Bronconeumol, 2010, 46(3): 135-142.
[10]
Lafferty EI, Qureshi ST, Schnare M. The role of toll like receptors in acute and chronic lung inflammation[J]. J Inflamm(Lond), 2010, 7: 57.
[11]
Ojaniemi M, Lijieroos M, Harju K, et al. TLR-2 is upregulated and mobilized to the hepatocyte plasma membrane in the space of Disse and to the Kupffer cells TLR-4 dependently during acute endotoxemia in mice[J]. Immunol Lett, 2006, 102(2): 158-168.
[12]
Hewison M. Vitamin D and immune function: an overview[J]. Proc Nutr Soc, 2012, 71(1): 50-61.
[13]
Holick MF, Chen TC. Vitamin D deficiency: a worldwide problem with health consequences[J]. Am J Clin Nutr, 2008, 87(4): 1080S-1086S.
[14]
Back O, Blomquist HK, Hernell O, et al. Does vitamin D intake during infancy promote the development of atopic allergy ?[J]. Acta Derm Venereol, 2009, 89(1): 28-32.
[15]
Mathieu C, Adorini L. The coming of age of 1, 25-dihydroxy vitamin D3 analogs as immunomodulatory agents[J]. Trends Mol Med, 2002, 8(4): 174-179.
[16]
Eftekharian MM, Zarnani AH, Moazzeni SM. In vivo effects of calcitriol on phenotypic and functional properties of dendritic cells[J]. Iran J Immunol, 2010, 7(2): 74-82.