Neuroendocrine cells derived chemokine vasoactive intestinal polypeptide (VIP) in allergic diseases

Abstract

Worldwide increase incidences of allergic diseases have heightened the interest of clinicians and researchers to understand the role of neuroendocrine cells in the recruitment and activation of inflammatory cells. Several pieces of evidence revealed the association of neuropeptides in the pathogenesis of allergic diseases. Importantly, one such peptide that is secreted by neuronal cells and immune cells exerts a wide spectrum of immunological functions as cytokine/chemokine is termed as Vasoactive Intestinal Peptide (VIP). VIP mediates immunological function through interaction with specific receptors namely VPAC-1, VPAC-2, CRTH2 and PAC1 that are expressed on several immune cells such as eosinophils, mast cells, neutrophils, and lymphocytes; therefore, provide the basis for the action of VIP on the immune system. Additionally, VIP mediated action varies according to target organ depending upon the presence of specific VIP associated receptor, involved immune cells and the microenvironment of the organ. Herein, we present an integrative review of the current understanding on the role of VIP and associated receptors in allergic diseases, the presence of VIP receptors on various immune cells with particular emphasis on the role of VIP in the pathogenesis of allergic diseases such as asthma, allergic rhinitis, and atopic dermatitis. Being crucial signal molecule of the neuroendocrine-immune network, the development of stable VIP analogue and/or antagonist may provide the future therapeutic drug alternative for the better treatment of these allergic diseases. Taken together, our current review summarizes the current understandings of VIP biology and further explore the significance of neuroendocrine cells derived VIP in the recruitment of inflammatory cells in allergic diseases that may be helpful to the investigators for planning the experiments and accordingly predicting new therapeutic strategies for combating allergic diseases. Summarized graphical abstract will help the readers to understand the significance of VIP in allergic diseases.

Keywords: Allergy; Asthma; EoE; Eosinophils; Mast cells; VIP.

Fig. 1

The summarized mechanistic events operational in VIP mediated signalling pathways. PKA =Protein kinase A; MAP kinase= Mitogen-activated protein kinase; CREB= cAMP response element binding protein; CBP= CRBP binding protein; NF-KB= Nuclear factor KB; TBP= TATA box binding protein; JAK/STAT= Janus kinase/signal transducer and activator of transcription; IκK=inhibitory κB kinase; LPS= Lipopolysaccharides; MEKK1= MAP/ERK kinase(MEK) KINASE 1; TLR= Toll-like receptor; STAT 1= Signal transducer and activator of transcription 1; JAK 1=Janus kinase 1;IRF 1=Interferon regulatory factor 1; PKC= Protein kinase C; DAG=Diacylglycerol; PIP2: Phosphatidylinositol 4,5-bisphosphate; PLC= Phospholipase C; IP3= Inositol 1,4,5 –triphosphate.

Fig. 2

The significance of VIP in asthma pathogenesis. Decreased VIP level in lungs leads to recruitment of inflammatory cells such as eosinophils, mast cells, neutrophils, lymphocytes in the lungs. These cells release the allergic mediators that promote airway inflammation and hyperresponsiveness. MBP=Major basic protein; ECP= Eosinophil cationic protein; EPO=Eosinophil peroxidase; LTs=Leukotrienes; TNF= Tumor necrosis factor; RANTES= regulated on activation, normal T cell expressed and secreted; TGF= Transforming growth factor; MPO=Myeloperoxidase; PAF=Platelet activating factor; GM-CSF=Granulocyte macrophage-colony stimulating factor.

Fig. 3

The significance of VIP in the pathogenesis of allergic rhinitis. Allergic mediators activate VIP-ergic nerves to induce the secretion of VIP which in turn promotes the trafficking of inflammatory cells in the tissue and manifest allergic responses. VCAM-1= Vascular cell adhesion molecule 1; TARC= Thymus-and activation Regulated chemokine; PGs=Prostaglandins; PGD2=Prostaglandin D2; DC=Dendritic cells; MCP-4=Monocyte chemotactic protein-4; EDN=Eosinophil-derived neurotoxin; MIP-1α=Macrophage Inflammatory Proteins -1α.