The herbal extract EPs® 7630 increases the antimicrobial airway defense through monocyte-dependent induction of IL-22 in T cells.
J Mol Med (Berl)
; 98(10): 1493-1503, 2020 10.
Article
em En
| MEDLINE
| ID: mdl-32948884
ABSTRACT
The phytotherapeutic compound EPs® 7630, an extract manufactured from Pelargonium sidoides roots, is frequently used for the treatment of airway infections. Nevertheless, the knowledge of the mode of action of EPs® 7630 is still sparse. Our study aimed at further elucidating the underlying pharmacological mechanisms by focusing on antimicrobial defense mechanisms of EPs® 7630. While investigating the influence of EPs® 7630 on lymphokine production by PBMCs, we found that EPs® 7630 is a novel inducer of IL-22 and IL-17. This cytokine-inducing effect was most pronounced for IL-22 and clearly dose-dependent starting from 1 µg/ml of the extract. Furthermore, EPs® 7630 pretreatment selectively enhanced the IL-22 and IL-17 production capacity of CD3/28-activated PBMCs while strongly limiting the IFN-γ production capacity of innate lymphoid cells. The relevance of EPs® 7630-induced IL-22 production was proven in vitro and in vivo, where IL-22 provoked a strong increase of the antimicrobial protein S100A9 in lung epithelial cells and pulmonary tissue, respectively. A detailed analysis of IL-22 induction modi revealed no direct influence of EPs® 7630 on the basal or anti-CD3/CD28 antibody-induced IL-22 production by CD4+ memory T cells. In fact, EPs® 7630-induced IL-22 production by CD4+ memory T cells was found to be essentially dependent on soluble mediators (IL-1/IL-23) as well as on direct cellular contact with monocytes. In summary, our study reveals a new immune-modulating function of EPs® 7630 that might confer IL-22 and IL-17-induced protection from bacterial airway infection. KEY MESSAGES EPs® 7630 selectively strengthens IL-22 and IL-17 production of memory T cells. EPs® 7630 limits the IFN-y production capacity of innate lymphoid cells. EPs® 7630-caused IL-22 production by T cells is essentially dependent on monocytes. IL-22 increase antimicrobial proteins (AMPs) in airway epithelium. EPs® 7630 might protect against airway infection by induction of AMP-inducers.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Extratos Vegetais
/
Monócitos
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Linfócitos T
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Interleucinas
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Anti-Infecciosos
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Mol Med (Berl)
Assunto da revista:
BIOLOGIA MOLECULAR
/
GENETICA MEDICA
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Alemanha