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Cyclooxygenase Inhibitors, Aspirin and Ibuprofen, Inhibit MHC-restricted Antigen Presentation in Dendritic Cells.

Kim HJ, Lee YH, Im SA, Kim K, Lee CK - Immune Netw (2010)

Bottom Line: In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens.Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs.These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.

ABSTRACT

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs).

Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells.

Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs.

Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

No MeSH data available.


DCs differentiated in the presence of aspirin or ibuprofen are suppressed in MHC class II-restricted antigen presentation capability. Indicated amounts of aspirin or ibuprofen were added to mouse bone marrow cells together with GM-CSF from the initiation of the DC differentiation-inducing culture (day0), at 3 days (Day3), or at 5 days (day5) after the initiation of the cultures. BM-DCs were harvested on day 6 from the initiation of the culture, and the ability to present exogenous antigen in association with MHC class II molecules was ascertained as in Fig. 2.
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Figure 3: DCs differentiated in the presence of aspirin or ibuprofen are suppressed in MHC class II-restricted antigen presentation capability. Indicated amounts of aspirin or ibuprofen were added to mouse bone marrow cells together with GM-CSF from the initiation of the DC differentiation-inducing culture (day0), at 3 days (Day3), or at 5 days (day5) after the initiation of the cultures. BM-DCs were harvested on day 6 from the initiation of the culture, and the ability to present exogenous antigen in association with MHC class II molecules was ascertained as in Fig. 2.

Mentions: To examine the effects of aspirin and ibuprofen on the acquisition of antigen presenting function, the drugs were added to DC differentiation-inducing cultures at different time points, days 0, 3 and 5 after the initiation of the culture. BM-DCs were harvested on day 6 from the initiation of the culture, and the ability to present exogenous antigen in association with MHC class II molecules was examined as in Fig. 2. As shown in Fig. 3A, DCs generated from mouse bone marrow cells in the presence of aspirin from the initiation of the culture (Day0) or 3 days after the initiation of the culture (Day3) were profoundly suppressed in MHC class II-restricted OVA presenting capability. This inhibitory effect of aspirin appeared to be dose dependent. When developing DCs were exposed to aspirin at a later time point (Day5, 5 days after the initiation of culture), the suppressive activity of aspirin on antigen presenting capability was weaker compared to the earlier exposures (Day0 and Day3). Likewise, DCs generated in the presence of ibuprofen from earlier time points of differentiation (Day0 and Day5) were significantly suppressed in MHC class II-restricted antigen presenting capability. We also found that DCs generated in the presence of aspirin or ibuprofen were suppressed in the MHC class I-restricted exogenous antigen presentation, and the suppressive activities of the drugs were more prominent when developing DCs were exposed to the drugs at earlier time points (data not shown).


Cyclooxygenase Inhibitors, Aspirin and Ibuprofen, Inhibit MHC-restricted Antigen Presentation in Dendritic Cells.

Kim HJ, Lee YH, Im SA, Kim K, Lee CK - Immune Netw (2010)

DCs differentiated in the presence of aspirin or ibuprofen are suppressed in MHC class II-restricted antigen presentation capability. Indicated amounts of aspirin or ibuprofen were added to mouse bone marrow cells together with GM-CSF from the initiation of the DC differentiation-inducing culture (day0), at 3 days (Day3), or at 5 days (day5) after the initiation of the cultures. BM-DCs were harvested on day 6 from the initiation of the culture, and the ability to present exogenous antigen in association with MHC class II molecules was ascertained as in Fig. 2.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2902675&req=5

Figure 3: DCs differentiated in the presence of aspirin or ibuprofen are suppressed in MHC class II-restricted antigen presentation capability. Indicated amounts of aspirin or ibuprofen were added to mouse bone marrow cells together with GM-CSF from the initiation of the DC differentiation-inducing culture (day0), at 3 days (Day3), or at 5 days (day5) after the initiation of the cultures. BM-DCs were harvested on day 6 from the initiation of the culture, and the ability to present exogenous antigen in association with MHC class II molecules was ascertained as in Fig. 2.
Mentions: To examine the effects of aspirin and ibuprofen on the acquisition of antigen presenting function, the drugs were added to DC differentiation-inducing cultures at different time points, days 0, 3 and 5 after the initiation of the culture. BM-DCs were harvested on day 6 from the initiation of the culture, and the ability to present exogenous antigen in association with MHC class II molecules was examined as in Fig. 2. As shown in Fig. 3A, DCs generated from mouse bone marrow cells in the presence of aspirin from the initiation of the culture (Day0) or 3 days after the initiation of the culture (Day3) were profoundly suppressed in MHC class II-restricted OVA presenting capability. This inhibitory effect of aspirin appeared to be dose dependent. When developing DCs were exposed to aspirin at a later time point (Day5, 5 days after the initiation of culture), the suppressive activity of aspirin on antigen presenting capability was weaker compared to the earlier exposures (Day0 and Day3). Likewise, DCs generated in the presence of ibuprofen from earlier time points of differentiation (Day0 and Day5) were significantly suppressed in MHC class II-restricted antigen presenting capability. We also found that DCs generated in the presence of aspirin or ibuprofen were suppressed in the MHC class I-restricted exogenous antigen presentation, and the suppressive activities of the drugs were more prominent when developing DCs were exposed to the drugs at earlier time points (data not shown).

Bottom Line: In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens.Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs.These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Chungbuk National University, Cheongju 361-763, Korea.

ABSTRACT

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used to relieve pain, reduce fever and inhibit inflammation. NSAIDs function mainly through inhibition of cyclooxygenase (COX). Growing evidence suggests that NSAIDs also have immunomodulatory effects on T and B cells. Here we examined the effects of NSAIDs on the antigen presenting function of dendritic cells (DCs).

Methods: DCs were cultured in the presence of aspirin or ibuprofen, and then allowed to phagocytose biodegradable microspheres containing ovalbumin (OVA). After washing and fixing, the efficacy of OVA peptide presentation by DCs was evaluated using OVA-specific CD8 and CD4 T cells.

Results: Aspirin and ibuprofen at high concentrations inhibited both MHC class I and class II-restricted presentation of OVA in DCs. In addition, the DCs generated in the presence of low concentrations of the drugs exhibit a profoundly suppressed capability to present MHC-restricted antigens. Aspirin and ibuprofen did not inhibit the phagocytic activity of DCs, the expression level of total MHC molecules and co-stimulatory molecules on DCs. Ibuprofen rather increased the expression level of total MHC molecules and co-stimulatory molecules on DCs.

Conclusion: These results demonstrate that aspirin and ibuprofen inhibit the intracellular processing event of the phagocytosed antigen, and further suggest that prolonged administration of NSAIDs in high doses may impair the capability of DCs to present antigens in asiociation with MHC molecules.

No MeSH data available.