Allergy Asthma Immunol Res.  2015 Sep;7(5):489-496. 10.4168/aair.2015.7.5.489.

Human Rhinovirus-induced Proinflammatory Cytokine and Interferon-beta Responses in Nasal Epithelial Cells From Chronic Rhinosinusitis Patients

• Kim JH
• Kim YS
• Cho GS
• Kim NH
• Gong CH
• Lee BJ
• Jang YJ

• KMID: 2147958
• DOI: http://doi.org/10.4168/aair.2015.7.5.489

Abstract

PURPOSE
Asthma exacerbation from human rhinovirus (HRV) infection is associated with deficient antiviral interferon (IFN) secretion. Although chronic rhinosinusitis (CRS), an inflammatory upper airway disease, is closely linked to asthma, IFN-beta responses to HRV infections in human nasal epithelial cells (HNECs) from CRS patients remain to be studied. We evaluated inflammatory and antiviral responses to HRV infection in HNECs from CRS patients.
METHODS
HNECs, isolated from turbinate tissue of 13 patients with CRS and 14 non-CRS controls, were infected with HRV16 for 4 hours. The HRV titer, LDH activity, production of proinflammatory cytokines and IFN-beta proteins, and expression levels of RIG-I and MDA5 mRNA were assessed at 8, 24, and 48 hours after HRV16 infection.
RESULTS
The reduction in viral titer was slightly delayed in the CRS group compared to the non-CRS control group. IL-6 and IL-8 were significantly increased to a similar extent in both groups after HRV infection. In the control group, IFN-beta production and MDA5 mRNA expression were significantly increased at 8 and 24 hours after HRV16 infection, respectively. By contrast, in the CRS group, IFN-beta was not induced by HRV infection; however, HRV-induced MDA5 mRNA expression was increased, but the increase was slightly delayed compared to the non-CRS control group. The RIG-I mRNA level was not significantly increased by HRV16 infection in either group.
CONCLUSIONS
HRV-induced secretion of proinflammatory cytokines in CRS patients was not different from that in the non-CRS controls. However, reductions in viral titer, IFN-beta secretion, and MDA5 mRNA expression in response to HRV infection in CRS patients were slightly impaired compared to those in the controls, suggesting that HRV clearance in CRS patients might be slightly deficient.

Keyword

Chronic rhinosinusitis; human rhinovirus; proinflammatory cytokine; interferon-beta; RNA helicase

MeSH Terms

Asthma
Cytokines
Epithelial Cells*
Humans
Interferon-beta*
Interferons
Interleukin-6
Interleukin-8
Rhinovirus
RNA Helicases
RNA, Messenger
Turbinates
Cytokines
Interferon-beta
Interferons
Interleukin-6
Interleukin-8
RNA Helicases
RNA, Messenger

Figure

• 

  Fig. 1 HRV16 viral titer and LDH activity in HNECs from controls and patients with CRS. (A) HRV16 release into the culture supernatant was determined by calculating the logTCID50/mL using a titration assay. The reduction in the HRV16 titer was slightly slower in the CRS group than in the controls, although there were no significant differences in the HRV16 titers between control subjects and patients with CRS at 8, 24, and 48 hours after HRV16 infection. †P<0.05, ††P<0.01. (B) LDH release from HNECs into the culture supernatant was measured. The increase in LDH activity was also slightly slower in the CRS group than in the controls, although there were no significant differences in LDH activity between the control group and the CRS group at 8, 24, and 48 hours after A HRV16 infection. *P<0.05; **P<0.01.

• 

  Fig. 2 Secretion of proinflammatory cytokines from HNECs into the culture supernatant. Levels of IL-6 (A) and IL-8 (B) at 8, 24, and 48 hours. IL-6 and IL-8 secretion were significantly increased to a similar extent in both CRS patients and controls after HRV16 infection, except for IL-6 levels at 48 hours and IL-8 levels at 8 hours. *P<0.05; **P<0.01; §P<0.05, control group compared with the CRS group.

• 

  Fig. 3 HRV16-induced IFN-β protein in HNECs. IFN-β was induced at 24 hours after HRV16 infection in the non-CRS control group. However, IFN-β expression was not significantly increased by HRV16 infection in the CRS groups. *P<0.05.

• 

  Fig. 4 RNA helicase mRNA expression in HNECs after HRV16 infection. (A) RIG-I mRNA was not significantly increased by HRV16 infection in either group. (B) MDA5 mRNA expression was significantly increased at 8 hours after HRV16 infection in the control group and at 24 hours in the CRS group. *P<0.05.

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