Coniferyl Aldehyde Inhibits the Inflammatory Effects of Leptomeningeal Cells by Suppressing the JAK2 Signaling

Abstract

Background. The brain is in many ways an immunologically and pharmacologically privileged site because of the blood-brain barrier (BBB). But for chronic peripheral inflammation, inflammatory signals can be transmitted from the peripheral system into the central nervous system (CNS) through multiple channels and result in neuroinflammation. Leptomeningeal cells that form the BBB can trigger one signaling pathway by releasing cytokines to transmit inflammatory signals. Besides, the Janus kinase (JAK) family may have a certain function in the activation of leptomeninges. In the present study, we try to use coniferyl aldehyde (CA), a natural anti-inflammatory phenolic compound, to inhibit this inflammatory process and elucidate the underlying molecular mechanisms. Results. Secretion of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) significantly increased after incubation with P. gingivalis. Moreover, TNF-α, IL-1β, and IL-6 levels were upregulated, and the JAK2 signaling was enhanced in leptomeningeal cells in a conditioned medium from activated macrophages, which leads to the immune response in microglia. However, this inflammatory effect of leptomeningeal cells was reversed by CA administration, accompanied by the decreased immune response in microglia. The western blot assay revealed that JAK2 phosphorylation was suppressed in leptomeningeal cells treated with CA. Conclusions. This study demonstrates that activated macrophages by P. gingivalis markedly induce the release of proinflammatory cytokines (TNF-α, IL-1β, and IL-6) from leptomeningeal cells, thereby activating the JAK2 signaling pathway and subsequently enhancing immune responses in microglia in the CNS. CA effectively inhibits the inflammatory effect of leptomeningeal cells via suppressing the JAK2 signaling pathway.

Coniferyl aldehyde alleviates LPS-induced WI-38 cell apoptosis and inflammation injury via JAK2–STAT1 pathway in acute pneumonia

“…Recently, some studies have suggested that CA can play an essential anti-inflammatory role. 4 However, CA is rarely studied in acute pneumonia, and understanding the molecular mechanism of CA in acute pneumonia could provide novel therapeutic targets for acute pneumonia. Nevertheless, the molecular mechanism of CA in determining acute pneumonia remains poorly understood.…”

“…3 In addition, CA has been reported to inhibit the inflammatory response of meningeal cells via inhibiting JAK2. 4 Moreover, CA alleviates ear edema induced by phorbol 12-myristate 13-acetate (TPA) in mice and inhibits excessive proliferation of epidermal and infiltration of white blood cells. Systemic application of CA significantly reduced carrageenan (CRG)-induced foot edema in rats, and CA had anti-inflammatory properties in vitro and in vivo by inhibiting JAK2-STAT1-iNOS signaling transduction.…”

Exploring ALDH2 expression and immune infiltration in HNSC and its correlation of prognosis with gender or alcohol intake

“…The functional enrichment analysis found that ALDH2 was related to the JAK-STAT pathway, indicating that the possible mechanism of the differential expression and prognostic value of ALDH2 in HNSC is related to the JAK-STAT pathway. A recent study has confirmed the inhibitory effect of aldehyde on the JAK2 signalling pathway through in vitro experiments 11 , further suggesting the possibility that ALDH2 participates in the JAK pathway. However, further experiments are needed to confirm the conclusions of this research.…”

Possible effects of Porphyromonas gingivalis on the blood–brain barrier in Alzheimer’s disease

“…Macrophages activated by P. gingivalis markedly induced production of TNF-α, IL-1β and IL-6 in leptomeningeal cells [28]. Wang et al [30] reported that in leptomeningeal cells P. gingivalis-induced reactive oxygen species, activated JAK2 and regulated production of inflammatory cytokines through c-Jun. A JAK2 inhibitor (coniferyl aldehyde) suppressed the pro-inflammatory reactions exerted by P. gingivalis-stimulated macrophages [30].…”

“…Wang et al [30] reported that in leptomeningeal cells P. gingivalis-induced reactive oxygen species, activated JAK2 and regulated production of inflammatory cytokines through c-Jun. A JAK2 inhibitor (coniferyl aldehyde) suppressed the pro-inflammatory reactions exerted by P. gingivalis-stimulated macrophages [30]. The JAK2/STAT3 axis in hippocampal neurons has been suggested as a novel target in the therapy patients with AD [31].…”