Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression through cyclooxygenase 2

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Hepatology. 2008 Jan 14 [Epub ahead of print]

Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression

through cyclooxygenase 2 signaling pathways.

Trujillo-Murillo K, Rincón-Sánchez AR, Martínez-Rodríguez H, Bosques-Padilla F,

Ramos-Jiménez J, Barrera-Saldaña HA, Rojkind M, Rivas-Estilla AM.

Department of Biochemistry, School of Medicine and University Hospital,

Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico.

It has been reported that salicylates (sodium salicylate and aspirin) inhibit

the replication of flaviviruses, such as Japanese encephalitis virus and dengue

virus. Therefore, we considered it important to test whether acetylsalicylic

acid (ASA) had anti-hepatitis C virus (HCV) activity. To this end, we examined

the effects of ASA on viral replication and protein expression, using an HCV

subgenomic replicon cell culture system. We incubated Huh7 replicon cells with

2-8 mM ASA for different times and measured HCV-RNA and protein levels by

northern blot, real-time polymerase chain reaction, and western analysis,

respectively. We found that ASA had a suppressive effect on HCV-RNA and protein

levels (nearly 58%). ASA-dependent inhibition of HCV expression was not mediated

by the 5'-internal ribosome entry site or 3'-untranslated regions, as determined

by transfection assays using bicistronic constructs containing these regulatory

regions. However, we found that HCV-induced cyclooxygenase 2 (COX-2) messenger

RNA and protein levels and activity and these effects were down-regulated by

ASA, possibly by a nuclear factor kappa B-independent mechanism. We also

observed that the ASA-dependent inhibition of viral replication was due in part

to inhibition of COX-2 and activation of p38 and mitogen-activated protein

kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2)

mitogen-activated protein kinases (MAPKs). Inhibition of these kinases by

SB203580 and U0126, respectively, and by short interfering RNA silencing of p38

and MEK1 MAPK prevented the antiviral effect of ASA. Taken together, our

findings suggest that the anti-HCV effect of ASA in the Huh7 replicon cells is

due to its inhibitory effect on COX-2 expression, which is mediated in part by

the activation of MEK1/2/p38 MAPK. Conclusion: These findings suggest the

possibility that ASA could be an excellent adjuvant in the treatment of chronic

HCV infection. (HEPATOLOGY 2008.).

PMID: 18393288 [PubMed - as supplied by publisher]

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[Guest guest]

Hepatology. 2008 Jan 14 [Epub ahead of print]

Acetylsalicylic acid inhibits hepatitis C virus RNA and protein expression

through cyclooxygenase 2 signaling pathways.

Trujillo-Murillo K, Rincón-Sánchez AR, Martínez-Rodríguez H, Bosques-Padilla F,

Ramos-Jiménez J, Barrera-Saldaña HA, Rojkind M, Rivas-Estilla AM.

Department of Biochemistry, School of Medicine and University Hospital,

Autonomous University of Nuevo Leon, Monterrey, Nuevo Leon, Mexico.

It has been reported that salicylates (sodium salicylate and aspirin) inhibit

the replication of flaviviruses, such as Japanese encephalitis virus and dengue

virus. Therefore, we considered it important to test whether acetylsalicylic

acid (ASA) had anti-hepatitis C virus (HCV) activity. To this end, we examined

the effects of ASA on viral replication and protein expression, using an HCV

subgenomic replicon cell culture system. We incubated Huh7 replicon cells with

2-8 mM ASA for different times and measured HCV-RNA and protein levels by

northern blot, real-time polymerase chain reaction, and western analysis,

respectively. We found that ASA had a suppressive effect on HCV-RNA and protein

levels (nearly 58%). ASA-dependent inhibition of HCV expression was not mediated

by the 5'-internal ribosome entry site or 3'-untranslated regions, as determined

by transfection assays using bicistronic constructs containing these regulatory

regions. However, we found that HCV-induced cyclooxygenase 2 (COX-2) messenger

RNA and protein levels and activity and these effects were down-regulated by

ASA, possibly by a nuclear factor kappa B-independent mechanism. We also

observed that the ASA-dependent inhibition of viral replication was due in part

to inhibition of COX-2 and activation of p38 and mitogen-activated protein

kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2)

mitogen-activated protein kinases (MAPKs). Inhibition of these kinases by

SB203580 and U0126, respectively, and by short interfering RNA silencing of p38

and MEK1 MAPK prevented the antiviral effect of ASA. Taken together, our

findings suggest that the anti-HCV effect of ASA in the Huh7 replicon cells is

due to its inhibitory effect on COX-2 expression, which is mediated in part by

the activation of MEK1/2/p38 MAPK. Conclusion: These findings suggest the

possibility that ASA could be an excellent adjuvant in the treatment of chronic

HCV infection. (HEPATOLOGY 2008.).

PMID: 18393288 [PubMed - as supplied by publisher]

_________________________________________________________________

Going green? See the top 12 foods to eat organic.

http://green.msn.com/galleries/photos/photos.aspx?gid=164 & ocid=T003MSN51N1653A