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MKP-1 negative regulates Staphylococcus aureus induced inflammatory responses in Raw264.7 cells: roles of PKA-MKP-1 pathway and enhanced by rolipram.


ABSTRACT: MAP phosphatases (MKP)-1 acts as an important regulator of innate immune response through a mechanism of control and attention both MAPK and NF-?B molecules during bacterial infection. However, the regulatory role of MKP-1 in the interplay between MAPK and NF?B pathway molecules is still not fully understood. In present study, we showed a direct interactions of p38, ERK or I?B? with MKP-1, and demonstrated that MKP-1 was a pivotal feedback control for both MAP kinases and NF-?B pathway in response to S. aureus. In addition, we found that rolipram had anti-inflammatory activity and repressed I?B? activation induced by S. aureus via PKA-MKP-1 pathway. Our report also demonstrated that PKA-c? can directly bind to I?B? upon S. aureus stimulation, which influenced the downstream signaling of PKA pathway, including altered the expression of MKP-1. These results presented a novel mechanism of PKA and I?B pathway, which may be targeted for treating S. aureus infection.

SUBMITTER: Pan Y 

PROVIDER: S-EPMC5620070 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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MKP-1 negative regulates Staphylococcus aureus induced inflammatory responses in Raw264.7 cells: roles of PKA-MKP-1 pathway and enhanced by rolipram.

Pan Yiqing Y   Xu Chen C   Pan Zhixing K ZK  

Scientific reports 20170928 1


MAP phosphatases (MKP)-1 acts as an important regulator of innate immune response through a mechanism of control and attention both MAPK and NF-κB molecules during bacterial infection. However, the regulatory role of MKP-1 in the interplay between MAPK and NFκB pathway molecules is still not fully understood. In present study, we showed a direct interactions of p38, ERK or IκBα with MKP-1, and demonstrated that MKP-1 was a pivotal feedback control for both MAP kinases and NF-κB pathway in respon  ...[more]

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