tetano
Editor, Senior Moderator
J Inflamm Res
. 2021 May 21;14:2121-2131.
doi: 10.2147/JIR.S312337. eCollection 2021.
In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
Ayman Mubarak[SUP] 1 [/SUP], Bahauddeen Alrfaei[SUP] 2 [/SUP], Abdullah Aljurayyan[SUP] 3 [/SUP], Mahfoudh M Alqafil[SUP] 1 [/SUP], Mohamed A Farrag[SUP] 1 [/SUP], Maaweya E Hamed[SUP] 1 [/SUP], Bandar Alosaimi[SUP] 4 [/SUP], Fahad Almajhdi[SUP] 1 [/SUP], Wael Alturaiki[SUP] 5 [/SUP]
Affiliations
Abstract
Background: Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in the Kingdom of Saudi Arabia, is associated with a high mortality rate.
Aim: To determine the effect of MERS-CoV on the immune response in infected patients and investigate cytokine production in the A549 epithelial cell line in response to a recombinant MERS-CoV spike protein (rSP) in the presence or absence of anti-dipeptidyl peptidase 4 (DPP4) antibody (3 independent experiments). Cytokine levels were measured using a cytokine ELISA array.
Methods: A Bio-Plex multiplex assay and cytokine ELISA were used in our study to measure the cytokine levels.
Results: Comparative analysis of MERS-CoV-infected patients (4 samples) and noninfected healthy controls (HCs) (5 samples) showed that serum levels of the following cytokines and chemokines were significantly higher in MERS-CoV patients than in the HCs (*p < 0.05): interferon (IFN)-α2 (43.4 vs 5.4), IFN-β (17.7 vs 6.2), IFN-γ (43.4 vs 9.7), interleukin (IL)-8 (13.7 vs 0), IL-2 (11.2 vs 3), IL-27p28 (57.8 vs 13.8), and IL-35 (167.5 vs 87.5).
Discussion: Our results revealed that MERS-CoV infection induced a slight increase in IFN levels but triggered a more pronounced increase in expression of the regulatory cytokines IL-27 and IL-35. A recombinant version of the full-length MERS-CoV spike protein increased the expression of IL-8 (160 pg/mL), IL-2 (100 pg/mL) and IL-12 (65 pg/mL) in A549 lung epithelial cells compared to that in the unstimulated control cells. The presence of anti-DPP4 antibody did not affect cytokine suppression or induction in A549 cells in vitro but decreased the level of IL-8 from 160 pg/mL to 65 pg/mL.
Conclusion: MERS-CoV can decrease IFN levels to interfere with the IFN pathway and enhance the production of regulatory cytokines. Inhibition of the increases in IL-27 and IL-35 may contribute to halting MERS-CoV in the early stage of infection.
Keywords: A549 lung cells; IFNs; MERS-CoV; anti-DPP4; proinflammatory cytokines; regulatory cytokines.
. 2021 May 21;14:2121-2131.
doi: 10.2147/JIR.S312337. eCollection 2021.
In vivo and in vitro Evaluation of Cytokine Expression Profiles During Middle East Respiratory Syndrome Coronavirus (MERS-CoV) Infection
Ayman Mubarak[SUP] 1 [/SUP], Bahauddeen Alrfaei[SUP] 2 [/SUP], Abdullah Aljurayyan[SUP] 3 [/SUP], Mahfoudh M Alqafil[SUP] 1 [/SUP], Mohamed A Farrag[SUP] 1 [/SUP], Maaweya E Hamed[SUP] 1 [/SUP], Bandar Alosaimi[SUP] 4 [/SUP], Fahad Almajhdi[SUP] 1 [/SUP], Wael Alturaiki[SUP] 5 [/SUP]
Affiliations
- PMID: 34045884
- PMCID: PMC8149276
- DOI: 10.2147/JIR.S312337
Abstract
Background: Middle East respiratory syndrome coronavirus (MERS-CoV) first emerged in the Kingdom of Saudi Arabia, is associated with a high mortality rate.
Aim: To determine the effect of MERS-CoV on the immune response in infected patients and investigate cytokine production in the A549 epithelial cell line in response to a recombinant MERS-CoV spike protein (rSP) in the presence or absence of anti-dipeptidyl peptidase 4 (DPP4) antibody (3 independent experiments). Cytokine levels were measured using a cytokine ELISA array.
Methods: A Bio-Plex multiplex assay and cytokine ELISA were used in our study to measure the cytokine levels.
Results: Comparative analysis of MERS-CoV-infected patients (4 samples) and noninfected healthy controls (HCs) (5 samples) showed that serum levels of the following cytokines and chemokines were significantly higher in MERS-CoV patients than in the HCs (*p < 0.05): interferon (IFN)-α2 (43.4 vs 5.4), IFN-β (17.7 vs 6.2), IFN-γ (43.4 vs 9.7), interleukin (IL)-8 (13.7 vs 0), IL-2 (11.2 vs 3), IL-27p28 (57.8 vs 13.8), and IL-35 (167.5 vs 87.5).
Discussion: Our results revealed that MERS-CoV infection induced a slight increase in IFN levels but triggered a more pronounced increase in expression of the regulatory cytokines IL-27 and IL-35. A recombinant version of the full-length MERS-CoV spike protein increased the expression of IL-8 (160 pg/mL), IL-2 (100 pg/mL) and IL-12 (65 pg/mL) in A549 lung epithelial cells compared to that in the unstimulated control cells. The presence of anti-DPP4 antibody did not affect cytokine suppression or induction in A549 cells in vitro but decreased the level of IL-8 from 160 pg/mL to 65 pg/mL.
Conclusion: MERS-CoV can decrease IFN levels to interfere with the IFN pathway and enhance the production of regulatory cytokines. Inhibition of the increases in IL-27 and IL-35 may contribute to halting MERS-CoV in the early stage of infection.
Keywords: A549 lung cells; IFNs; MERS-CoV; anti-DPP4; proinflammatory cytokines; regulatory cytokines.