RESUMO
The dysfunction of regulatory B cells (Breg) may result in immune inflammation such as allergic rhinitis (AR); the underlying mechanism is not fully understood yet. Short-chain fatty acids, such as propionic acid (PA), have immune regulatory functions. This study is aimed at testing a hypothesis that modulates PA production alleviating airway allergy through maintaining Breg functions. B cells were isolated from the blood obtained from AR patients and healthy control (HC) subjects. The stabilization of IL-10 mRNA in B cells was tested with RT-qPCR. An AR mouse model was developed to test the role of PA in stabilizing the IL-10 expression in B cells. We found that the serum PA levels were negatively correlated with the serum Th2 cytokine levels in AR patients. Serum PA levels were positively associated with peripheral CD5+ B cell frequency in AR patients; the CD5+ B cells were also IL-10+. The spontaneous IL-10 mRNA decay was observed in B cells, which was prevented by the presence of PA through activating GPR43. PA counteracted the effects of Tristetraprolin (TTP) on inducing IL-10 mRNA decay in B cells through the AKT/T-bet/granzyme B pathway. Administration of Yupinfeng San, a Chinese traditional medical formula, or indole-3-PA, induced PA production by intestinal bacteria to stabilize the IL-10 expression in B cells, which promoted the allergen specific immunotherapy, and efficiently alleviated experimental AR. In summary, the data show that CD5+ B cells produce IL-10. The serum lower PA levels are associated with the lower frequency of CD5+ B cells in AR patients. Administration with Yupinfeng San or indole-3-PA can improve Breg functions and alleviate experimental AR.
Assuntos
Linfócitos B Reguladores/imunologia , Dessensibilização Imunológica , Propionatos/metabolismo , Rinite Alérgica/terapia , Adolescente , Adulto , Animais , Linfócitos B Reguladores/metabolismo , Estudos de Casos e Controles , Células Cultivadas , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Feminino , Microbioma Gastrointestinal/imunologia , Voluntários Saudáveis , Humanos , Indóis/administração & dosagem , Interleucina-10/genética , Interleucina-10/metabolismo , Masculino , Camundongos , Pessoa de Meia-Idade , Cultura Primária de Células , Propionatos/sangue , Estabilidade de RNA , Receptores de Superfície Celular/metabolismo , Rinite Alérgica/sangue , Rinite Alérgica/imunologia , Células Th2/imunologia , Células Th2/metabolismo , Adulto JovemRESUMO
Two novel diterpenes, norcaesalpinin I (1) featuring an unusual ring C-contracted dinorcassane and caesalpinin U (2) possessing a highly oxygenated furanocassane skeleton were isolated from the seeds of Caesalpinia minax. Their structures were determined by different spectroscopic methods. A plausible biosynthetic pathway of 1 was proposed. The cytotoxic activity of compounds 1 and 2 against HepG2 and HeLa human tumor cell lines was evaluated.