Semaphorin 7A is expressed on airway eosinophils and upregulated by IL-5 family cytokines

Abstract

Semaphorin 7A (Sema7A) plays a major role in TGF-β1-induced lung fibrosis. Based on the accumulating evidence that eosinophils contribute to fibrosis/remodeling in the airway, we hypothesized that airway eosinophils may be a significant source of sema7A. In vivo, sema7A was expressed on the surface of circulating eosinophils and upregulated on bronchoalveolar lavage eosinophils obtained after segmental bronchoprovocation with allergen. Based on mRNA levels in unfractionated and isolated bronchoalveolar cells, eosinophils are the predominant source of sema7A. In vitro, among the members of the IL-5-family cytokines, sema7A protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5. Cytokine-induced expression of cell surface sema7A required translation of newly synthetized protein. Finally, a recombinant sema7A induced alpha-smooth muscle actin production in human bronchial fibroblasts. Semaphorin 7A is a potentially important modulator of eosinophil profibrotic functions in the airway remodeling of patients with chronic asthma.

Semaphorin 7A plays a critical role in IgE-mediated airway inflammation in mice

“…The expression of SEMA7A in the lungs of IgE-sensitized mice was increased compared with that in nonsensitized mice; consistent with previous data (Holmes et al, 2002;Sato and Takahashi, 1998;Mine et al, 2000;Esnault et al, 2014), the epithelial cells, blood vessels, and inflammatory cells in the lungs of IgEsensitized mice showed this expression. Furthermore, it has been reported that SEMA7A facilitates increased transendothelial migration of neutrophils depending on the PLXNC1 for the receptor (Morote-Garcia et al, 2012); PLXNC1 is expressed in neutrophils in peripheral blood of normal mice , and is associated with adhesion in the inflammatory cell transmigration process (Holmes et al, 2002;Lazova et al, 2009).…”

“…Among them, semaphorin 7A (SEMA7A) was originally shown to promote axon outgrowth and contribute to the formation of lateral olfactory tracts (Pasterkamp et al, 2003). However, SEMA7A is expressed broadly by lymphoid cells, eosinophils, myeloid cells, bone cells, the nervous system, epidermal keratinocytes, fibroblasts, and endothelial blood vessels (Holmes et al, 2002;Sato and Takahashi, 1998;Mine et al, 2000;Esnault et al, 2014). Additionally, it is a potent stimulator of monocytes and neutrophils and induces cytokine production (Holmes et al, 2002); T-cell responses are negatively regulated by it (Czopik et al, 2006), suggesting the possibility that SEMA7A contributes to the development of allergic diseases.…”

Effects of combined progesterone and 17β-estradiol treatment on the transcriptome of cultured human myometrial smooth muscle cells

“…In uterine smooth muscle cells myocyte enhancer factor 2 is also bound in this complex (57). Previous studies have also reported the upregulation of several transcription factors associated with the transition from pregnant not-in-labor to laboring myometrium in rat, mouse and human (8,16,25,28,32,53,62,69).…”

Semaphorin 4D is expressed constitutively by human eosinophils

“…We used the several cytokines (IL-3, IL-5, GM-CSF, TNF-a, b-NGF, and VEGF) which were reported the activated effect for eosinophils or the enhanced expression for semaphorin receptors for priming. 10,11 There is a possibility that up-regulation of semaphorin receptors and direct effect of semaphorin are led in eosinophils by other priming methods. Previous study reported that sema7A expressed on eosinophils and sema7A protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5.…”

“…Previous study reported that sema7A expressed on eosinophils and sema7A protein on the surface of blood eosinophils was increased more by IL-3 than by GM-CSF or IL-5. 10 Peer review under responsibility of Japanese Society of Allergology.…”