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An ADP ribosylation factor-GTPase activating protein negatively regulates the production of proinflammatory mediators in response to lipopolysaccharide

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Abstract

An ADP ribosylation factor-GTPase activating protein (ASAP1) is highly expressed in a variety of tumor cells and is involved in the cell motility, invasion, and metastasis. In order to elucidate the involvement of ASAP1 in lipopolysaccharide (LPS)-mediated inflammatory response, the effect of ASAP1 silencing on LPS-induced proinflammatory mediators production was examined by using RAW 264.7 macrophage-like cells. ASAP1 was constitutively expressed in the cells and the expression was augmented by LPS stimulation. Silencing of ASAP1 with small interfering RNA enhanced the production of tumor necrosis factor-α, interleukin 6, interferon-β, and nitric oxide in response to LPS. ASAP1 silencing augmented the activation of nuclear factor (NF)-κB and several mitogen-activated protein kinases (MAPKs). On the other hand, ASAP1 silencing did not affect the expression of IRAK4, TRAF6, and Akt as the upstream molecules of NF-κB signaling. A series of toll-like receptor ligands as well as LPS augmented the ASAP1 expression. Taken together, ASAP1 was suggested to negatively regulate LPS-induced proinflammatory mediators production through down-regulating LPS signaling. The feedback function of ASAP1 in LPS-mediated inflammatory response is discussed.

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Abbreviations

ASAP1:

ADP ribosylation factor (Arf)-GTPase activating protein

ERK1/2:

Extracellular signal-regulated kinase 1/2

ELISA:

Enzyme-linked immunosorbent assay

GAPDH:

Glyceraldehyde 3-phosphate dehydrogenase

IFN-β:

Interferon-β

IKK:

IκB kinase

IRAK4:

Interleukin-1 receptor-associated kinase-4

JNK:

c-Jun N-terminal kinase

LPS:

Lipopolysaccharide

MAPK:

Mitogen-activated protein kinase

MyD88:

Myeloid differentiation factor 88

NF-κB:

Nuclear factor-κB

NO:

Nitric oxide

RT–PCR:

Reverse transcription-polymerase chain reaction

SAPK:

Stress-activated protein kinase

siRNA:

Small interfering RNA

TLR:

Toll-like receptor

TNF-α:

Tumor necrosis factor-α

TRAF6:

TNF receptor-associated factor 6

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Acknowledgments

This work was supported by in part by a Grant-in-Aid for Scientific Research from the Ministry of Education, Science, Sports and Culture of Japan. We are grateful to K. Takahashi and A. Morikawa for the technical assistance.

Conflict of interest

The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

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Authors and Affiliations

  1. Department of Microbiology and Immunology, Aichi Medical University School of Medicine, Nagakute, Aichi, 480-1195, Japan

    Abedul Haque, Abu Shadat Mohammod Noman, Naoki Koide, Erdenezaya Odkhuu, Yoshikazu Naiki, Shoji Hashimoto, Takayuki Komatsu, Tomoaki Yoshida & Takashi Yokochi

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  1. Abedul Haque
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  2. Abu Shadat Mohammod Noman
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  3. Naoki Koide
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  4. Erdenezaya Odkhuu
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  5. Yoshikazu Naiki
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  6. Shoji Hashimoto
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  7. Takayuki Komatsu
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  8. Tomoaki Yoshida
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  9. Takashi Yokochi
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Corresponding author

Correspondence to Takashi Yokochi.

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Haque, A., Noman, A.S.M., Koide, N. et al. An ADP ribosylation factor-GTPase activating protein negatively regulates the production of proinflammatory mediators in response to lipopolysaccharide. Cancer Immunol Immunother 60, 1439–1446 (2011). https://doi.org/10.1007/s00262-011-1048-9

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  • DOI: https://doi.org/10.1007/s00262-011-1048-9

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