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. 2018 Sep;12(5):662-666.
doi: 10.1111/irv.12561. Epub 2018 May 22.

Increase in CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells

Steffen Kunzmann  1   2 , Christine Krempl  3 , Silvia Seidenspinner  2 , Kirsten Glaser  2 , Christian P Speer  2 , Markus Fehrholz  2
Affiliations

Increase in CTGF mRNA expression by respiratory syncytial virus infection is abrogated by caffeine in lung epithelial cells

Steffen Kunzmann et al. Influenza Other Respir Viruses. 2018 Sep.

Abstract

Respiratory syncytial virus (RSV) is a leading cause of severe lower respiratory tract infection in early childhood. Underlying pathomechanisms of elevated pulmonary morbidity in later infancy are largely unknown. We found that RSV-infected H441 cells showed increased mRNA expression of connective tissue growth factor (CTGF), a key factor in airway remodeling. Additional dexamethasone treatment led to further elevated mRNA levels, indicating additive effects. Caffeine treatment prevented RSV-mediated increase in CTGF mRNA. RSV may be involved in airway remodeling processes by increasing CTGF mRNA expression. Caffeine might abrogate these negative effects and thereby help to restore lung homeostasis.

Keywords: CCN2; Caffeine; dexamethasone; lung remodeling; poly(I:C).

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Figures

Figure 1
Figure 1
Infection of H441 and IMR‐90 cells with rgRSV and increase in inflammatory markers. H441 and IMR‐90 were either left untreated or infected with rgRSV and after 2 hour treated with 1 μmol/L dexamethasone for 24 hour. qPCR specific for IL‐6 and IL‐8 mRNA was performed. Images of H441 (A) and IMR‐90 cells (B) 24 hour post‐infection with rgRSV. Virus infection is visible by expression of GFP (lower panel), cell morphology of infected cells in brightfield (upper panel). IL‐6 (C and D) and IL‐8 (E and F) mRNA levels of H441 (C and E) and IMR‐90 cells (D and F), respectively, were normalized to GAPDH mRNA and fold differences compared to corresponding untreated cells were calculated. Means + SD of n = 4 independent experiments are shown. *P < .05; **P < .01; ***P < .001 compared to untreated controls; # P < .05; ## P < .01; ### P < .001 compared to cells treated with dexamethasone; $$$ P < .001 compared to cells infected with rgRSV
Figure 2
Figure 2
Increase in connective tissue growth factor (CTGF) mRNA expression by dexamethasone and rgRSV in H441 and by dexamethasone in IMR‐90 cells is abrogated by caffeine treatment. H441 and IMR‐90 cells were either left untreated or infected with rgRSV and after 2 hour treated with 1 μmol/L dexamethasone and/or 10 mmol/L caffeine for 24 hour. qPCR of CTGF mRNA was performed, CTGF mRNA levels of H441 cells (A) and IMR‐90 cells (B) were normalized to GAPDH mRNA, and fold differences compared to untreated cells were calculated. Means + SD of n ≥ 3 independent experiments are shown. **P < .01; ***P < .001 compared to corresponding controls; ### P < .001 compared to corresponding cells treated with dexamethasone; $$$ P < .001 compared to corresponding cells infected with rgRSV
Figure 3
Figure 3
Poly(I:C) increases mRNA expression of inflammatory markers and connective tissue growth factor (CTGF) in H441 cells. H441 cells were either treated with PEI alone or transfected with 10 μg/mL poly(I:C) and after 4 hour treated with 1 μmol/L dexamethasone for 24 hour. qPCR against IL‐6 (A) IL‐8 (B), and CTGF (C) mRNA was performed. mRNA levels were normalized to GAPDH and fold differences compared to untreated cells were calculated. Means + SD of n = 3 independent experiments are shown. *P < .05; **P < .01; ***P < .001 compared to untreated controls; # P < .05; ## P < .01; ### P < .001 compared to cells treated with dexamethasone
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References

    1. Openshaw PJM, Chiu C, Culley FJ, Johansson C. Protective and harmful immunity to RSV infection. Annu Rev Immunol. 2017;35:501‐532. - PubMed
    1. Piedimonte G. RSV infections: state of the art. Cleve Clin J Med. 2015;82:03. - PubMed
    1. Kubota S, Takigawa M. Cellular and molecular actions of CCN2/CTGF and its role under physiological and pathological conditions. Clin Sci. 2015;128:181‐196. - PubMed
    1. Alapati D, Rong M, Chen S, et al. Connective tissue growth factor antibody therapy attenuates hyperoxia‐induced lung injury in neonatal rats. Am J Respir Cell Mol Biol. 2011;45:1169‐1177. - PubMed
    1. Pan LH, Yamauchi K, Uzuki M, et al. Type II alveolar epithelial cells and interstitial fibroblasts express connective tissue growth factor in IPF. Eur Respir J. 2001;17:1220‐1227. - PubMed

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