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KMID : 0624620110440050329
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BMB Reports
2011 Volume.44 No. 5 p.329 ~ p.334
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Levosulpiride, (S)-(-)-5-Aminosulfonyl-N-[(1-ethyl-2-pyrrolidinyl) methyl]-2-methoxybenzamide, enhances the transduction efficiency of PEP-1-ribosomal protein S3 in vitro and in vivo
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Ahn Eun-Hee
Kim Dae-Won
Kim Duk-Soo
Woo Su-Jung
Kim Hye-Ri
Kim Joon
Lim Soon-Sung
Kang Tae-Cheon
Kim Dong-Joon
Suk Ki-Tae
Park Jin-Seu
Luo Qiuxiang
Eum Won-Sik
Hwang Hyun-Sook
Choi Soo-Young
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Abstract
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Many proteins with poor transduction efficiency were reported to be delivered to cells by fusion with protein transduction domains (PTDs). In this study, we investigated the effect of levosulpiride on the transduction of PEP-1 ribosomal protein S3 (PEP-1-rpS3), and examined its influence on the stimulation of the therapeutic properties of PEP-1-rpS3. PEP-1-rpS3 transduction into HaCaT human keratinocytes and mouse skin was stimulated by levosulpiride in a manner that did not directly affect the cell viability. Following 12-O-tetradecanoylphorbol- 13-acetate (TPA)-induced inflammation in mice, levosulpiride alone was ineffective in reducing TPA-induced edema and in inhibiting the elevated productions of inflammatory mediators and cytokines, such as cyclooxygenase-2, inducible nitric oxide synthase, interleukin-6 and -1β, and tumor necrosis factor- α. Anti-inflammatory activity by PEP-1-rpS3 + levosulpiride was significantly more potent than by PEP-1-rpS3 alone. These results suggest that levosulpiride may be useful for enhancing the therapeutic effect of PEP-1-rpS3 against various inflammatory diseases.
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KEYWORD
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Inflammation, Levosulpiride, PEP-1-rpS3, Protein therapy, Protein transduction
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