CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells
Objective. The effects of C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) on pregnancy-associated plasma protein-A (PAPP-A) expression in human peripheral blood mononuclear cells (PBMCs) require further investigation. Methods. The PAPP-A levels in culture supernatants, PAPP-A mRNA expre...
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2012/697832 |
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| _version_ | 1832565154123874304 |
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| author | Weiping Li Hongwei Li Fusheng Gu |
| author_facet | Weiping Li Hongwei Li Fusheng Gu |
| author_sort | Weiping Li |
| collection | DOAJ |
| description | Objective. The effects of C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) on pregnancy-associated plasma protein-A (PAPP-A) expression in human peripheral blood mononuclear cells (PBMCs) require further investigation. Methods. The PAPP-A levels in culture supernatants, PAPP-A mRNA expression, and cellular PAPP-A expression were measured in human PBMCs isolated from fresh blood donations provided by 6 healthy volunteers (4 donations per volunteer). Analyses were conducted by ultrasensitive ELISA, western blotting, and RT-PCR following stimulation with CRP or TNF-α cytokines. Results. PAPP-A mRNA and protein levels after CRP stimulation peaked at 24 hours, whereas peak PAPP-A mRNA and protein levels were achieved after TNF-α stimulation at only 2 and 8 hours, respectively. These findings indicate the dose-dependent effect of CRP and TNF-α stimulation. Actinomycin D treatment completely prevented CRP and TNF-α induction of PAPP-A mRNA and protein expression. Additionally, nuclear factor- (NF-) κB inhibitor (BAY11-7082) potently inhibited both CRP and TNF-α stimulated PAPP-A mRNA and protein expression. Conclusions. Human PBMCs are capable of expressing PAPP-A in vitro, expression that may be regulated by CRP and TNF-α through the NF-κB pathway. This mechanism may play a significant role in the observed increase of serum PAPP-A levels in acute coronary syndrome (ACS). |
| format | Article |
| id | doaj-art-3285ea5e852145e2b1a9cf1f83228a7d |
| institution | Kabale University |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-3285ea5e852145e2b1a9cf1f83228a7d2025-02-03T01:09:05ZengWileyMediators of Inflammation0962-93511466-18612012-01-01201210.1155/2012/697832697832CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear CellsWeiping Li0Hongwei Li1Fusheng Gu2Department of Cardiology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, ChinaDepartment of Cardiology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, ChinaDepartment of Cardiology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, ChinaObjective. The effects of C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) on pregnancy-associated plasma protein-A (PAPP-A) expression in human peripheral blood mononuclear cells (PBMCs) require further investigation. Methods. The PAPP-A levels in culture supernatants, PAPP-A mRNA expression, and cellular PAPP-A expression were measured in human PBMCs isolated from fresh blood donations provided by 6 healthy volunteers (4 donations per volunteer). Analyses were conducted by ultrasensitive ELISA, western blotting, and RT-PCR following stimulation with CRP or TNF-α cytokines. Results. PAPP-A mRNA and protein levels after CRP stimulation peaked at 24 hours, whereas peak PAPP-A mRNA and protein levels were achieved after TNF-α stimulation at only 2 and 8 hours, respectively. These findings indicate the dose-dependent effect of CRP and TNF-α stimulation. Actinomycin D treatment completely prevented CRP and TNF-α induction of PAPP-A mRNA and protein expression. Additionally, nuclear factor- (NF-) κB inhibitor (BAY11-7082) potently inhibited both CRP and TNF-α stimulated PAPP-A mRNA and protein expression. Conclusions. Human PBMCs are capable of expressing PAPP-A in vitro, expression that may be regulated by CRP and TNF-α through the NF-κB pathway. This mechanism may play a significant role in the observed increase of serum PAPP-A levels in acute coronary syndrome (ACS).http://dx.doi.org/10.1155/2012/697832 |
| spellingShingle | Weiping Li Hongwei Li Fusheng Gu CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells Mediators of Inflammation |
| title | CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells |
| title_full | CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells |
| title_fullStr | CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells |
| title_full_unstemmed | CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells |
| title_short | CRP and TNF-α Induce PAPP-A Expression in Human Peripheral Blood Mononuclear Cells |
| title_sort | crp and tnf α induce papp a expression in human peripheral blood mononuclear cells |
| url | http://dx.doi.org/10.1155/2012/697832 |
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