Ethanol, TLR3, and TLR4 Agonists Have Unique Innate Immune Responses in Neuron‐Like SH‐SY5Y and Microglia‐Like BV2

نویسندگان

  • Colleen J Lawrimore
  • Fulton T Crews
چکیده

BACKGROUND Ethanol (EtOH) consumption leads to an increase of proinflammatory signaling via activation of Toll-like receptors (TLRs) such as TLR3 and TLR4 that leads to kinase activation (ERK1/2, p38, TBK1), transcription factor activation (NFκB, IRF3), and increased transcription of proinflammatory cytokines such as TNF-α, IL-1β, and IL-6. This immune signaling cascade is thought to play a role in neurodegeneration and alcohol use disorders. While microglia are considered to be the primary macrophage in brain, it is unclear what if any role neurons play in EtOH-induced proinflammatory signaling. METHODS Microglia-like BV2 and retinoic acid-differentiated neuron-like SH-SY5Y were treated with TLR3 agonist Poly(I:C), TLR4 agonist lipopolysaccharide (LPS), or EtOH for 10 or 30 minutes to examine proinflammatory immune signaling kinase and transcription factor activation using Western blot, and for 24 hours to examine induction of proinflammatory gene mRNA using RT-PCR. RESULTS In BV2, both LPS and Poly(I:C) increased p-ERK1/2, p-p38, and p-NFκB by 30 minutes, whereas EtOH decreased p-ERK1/2 and increased p-IRF3. LPS, Poly(I:C), and EtOH all increased TNF-α and IL-1β mRNA, and EtOH further increased TLR2, 7, 8, and MD-2 mRNA in BV2. In SH-SY5Y, LPS had no effect on kinase or proinflammatory gene expression. However, Poly(I:C) increased p-p38 and p-IRF3, and increased expression of TNF-α, IL-1β, and IL-6, while EtOH increased p-p38, p-IRF3, p-TBK1, and p-NFκB while decreasing p-ERK1/2 and increasing expression of TLR3, 7, 8, and RAGE mRNA. HMGB1, a TLR agonist, was induced by LPS in BV2 and by EtOH in both cell types. EtOH was more potent at inducing proinflammatory gene mRNA in SH-SY5Y compared with BV2. CONCLUSIONS These results support a novel and unique mechanism of EtOH, TLR3, and TLR4 signaling in neuron-like SH-SY5Y and microglia-like BV2 that likely contributes to the complexity of brain neuroimmune signaling.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

I-23: Reproduction and Toll Like Receptors(TLRs

Female and male reproductive tracts are of interest sites to study of immune system because they encounter specific infections such as those are sexually transmitted. Furthermore, female reproductive tract is in close contact with allogenic sperms and transmitted microorganisms during intercourse and semi allogenic fetus during pregnancy. In mammals, there are two types of immune responses, the...

متن کامل

Inflammatory cytokines responses of common carp, Cyprinus carpio, leucocytes in vitro treated by immunostimulants

Cytokines are important regulators of the immune system, and identifying fish cytokines has potential applications for the development of vaccines and/or immunostimulants application in fisheries. In order to understand the immune-related genes triggered by immunostimulants derived from pathogens, we investigated the effects of agonists (lipopolysaccharide (LPS), Poly I:C, and imiquimod) of thr...

متن کامل

Different Tlr Agonists Tend to Elicit an Immune- Regulatory Cytokine and Chemokine Phenotype in Human Microglia Submitted for Publication

Microglia, the macrophage-like cells in the CNS, express different TLRs that recognize conserved microbial structures and endogenous danger signals. Preliminary studies have indicated that human microglia cells express a wide range of different TLR family members as opposed to astrocytes and oligodendrocytes which primarily express TLR2, TLR3 and TLR4. Here, we show that cultured human microgli...

متن کامل

P108: Microglia in Traumatic Brain Injury

Microglia is one of the first innate immune components. These cells account about 5 to 10% of the entire adult brain cells and are activated by trauma. Complex-mediated inflammatory responses occur through cellular and molecular events during and after the traumatic brain injury (TBI). In-lesion area astrocytes, microglia, and damaged neurons begin to secrete cytokines and chemokines. Microglia...

متن کامل

Broad expression of Toll-like receptors in the human central nervous system.

The family of Toll-like receptors (TLRs) plays a key role in controlling innate immune responses to a wide variety of pathogen-associated molecules. In this study we investigated expression of TLRs in vitro by purified human microglia, astrocytes, and oligodendrocytes, and in vivo by immunohistochemical examination of brain and spinal cord sections. Cultured primary microglia were found to expr...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 41  شماره 

صفحات  -

تاریخ انتشار 2017