Evaluation of anti-pruritic effects of ITCs that inhibit TLR3 signaling

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  • Moriyama Masaki
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan
  • Konno Mitsuhiro
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan
  • Serizawa Kanako
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan
  • Yuzawa Natsumi
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan
  • Majima Yuki
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan
  • Hayashi Ikuo
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan
  • Suzuki Tomohiko
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan
  • Kainoh Mie
    Pharmaceutical Research Laboratories, Toray Industries, Inc., Japan

Description

<p>The role of innate immune system as mediators of neuro-immune communication and therapeutic targets for itch is emerging. TLR3 has an important role for itch as shown in TLR3 knock out mice. In this study, to evaluate effects of TLR3 inhibitors on histamine-independent itch, we used two kinds of isothiocyanate (ITC). Both Phenethyl isothiocyanate (PEITC) and Sulforaphane (SFN) inhibited Poly I:C (PIC)-induced signaling in RAW264.7 cell line. Then, we evaluated anti-pruritic effect of these compounds on PIC- and Chloroquine (CQ)-induced scratching behavior. PEITC suppressed both PIC- and CQ-evoked scratching behavior. Whereas SFN also inhibited PIC-induced acute itch. Finally we have tested with oxazolone-induced chronic itch model mice. Surprisingly oral dosing of both compounds suppressed scratching behaviors that were observed in mice. Our findings demonstrate that TLR3 is a critical mediator in acute and chronic itch transduction in mice and may be a promising therapeutic target for pruritus disorders. It is noteworthy that SFN is expected to be applied to as an antipruritic since it's a phytochemical used as a supplement.</p>

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