RESUMO
Toll-like receptor 9 (TLR9) plays a major role in the fight against DNA viruses infections. Despite its antitumor properties, inappropriate activation of TLR9 during chronic inflammation may cause the activation of transcription factors inducing pro-cancerous activities. Thus, the relationship between TLR9 and cancer remains highly confrontational especially in gynecological cancers and cervical cancer induced by viruses. In this review, we focus on the beneficial and detrimental role of TLR9 in gynecological carcinogenesis. TLR9 contributes to tumor regression by inducing cytotoxic T cell response (CTL), reducing the numbers of myeloid-derived suppressor cells (MDSCs), the tumor-associated macrophages (TAMs) and the regulatory T cells (T regs). It can however, also promote tumor progression and invasiveness of cervical tissue. Therefore, the dichotomous role of TLR9 needs to be carefully investigated in the setting of neoplastic disease.
Assuntos
Neoplasias dos Genitais Femininos/imunologia , Proteínas de Neoplasias/fisiologia , Receptor Toll-Like 9/fisiologia , Carcinogênese , Progressão da Doença , Feminino , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/virologia , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Inflamação , Macrófagos/imunologia , Células Supressoras Mieloides/imunologia , NF-kappa B/metabolismo , Invasividade Neoplásica , Neovascularização Patológica/fisiopatologia , Papillomaviridae/patogenicidade , Infecções por Papillomavirus/imunologia , Linfócitos T Reguladores/imunologia , Receptor Toll-Like 9/agonistasRESUMO
Numerous toxins from scorpion venoms are much more toxic to insects than to other animal classes, and possess high affinity to Na+ channels. Many of them active on insects were purified from the venom of Buthus occitanus tunetanus. Using amino acid sequences of BotIT2 and RACE-PCR amplification (Rapid amplification of cDNA ends) technique, we isolated, identified and sequenced the nucleotide sequence from the venom glands of the scorpion Buthus occitanus tunetanus. The cDNA encodes a precursor of an insect toxin of 60 amino acid residues. The deduced nucleotide sequence toxin was identical to the determined amino acid sequence of BotIT2. BotIT2 is more similar to the excitatory toxins in its mode of action and to the depressant toxins in its primary structure.
Assuntos
Sequência de Bases/genética , Clonagem Molecular/métodos , Venenos de Escorpião/genética , Sequência de Aminoácidos , Substituição de Aminoácidos/genética , Animais , Western Blotting , DNA Complementar/genética , Eletroforese em Gel de Ágar , Eletroforese em Gel de Poliacrilamida , Expressão Gênica/genética , Insetos/efeitos dos fármacos , Dados de Sequência Molecular , Neurotoxinas/efeitos adversos , Neurotoxinas/química , Técnica de Amplificação ao Acaso de DNA Polimórfico , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Venenos de Escorpião/efeitos adversos , Venenos de Escorpião/química , Venenos de Escorpião/classificação , Venenos de Escorpião/isolamento & purificação , Escorpiões , Canais de Sódio/efeitos dos fármacos , Relação Estrutura-Atividade , TunísiaRESUMO
We report the use of recombinant scorpion toxin in the form of fusion protein as antigen for mice immunisation. The aim is to produce protective antisera against lethal activity of the venom from Tunisian scorpion Buthus occitanus tunetanus, responsible for several annually reported human cases of scorpion stings. The gene encoding Bot III (the most toxic alpha toxin of Buthus occitanus tunetanus) was fused to the sequence encoding synthetic ZZ domains of staphylococcal protein A. The construct ZZ-Bot III was expressed in the periplasm of E. coli as a fusion protein and purified by affinity chromatography. The recombinant fusion protein was characterized and used as antigen to generate antibodies in mice. The antibodies against the recombinant protein neutralize the toxic venom (10 LD50/ml) and also confer protection for immunized mice against antigenically related mammal toxins.
