Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury.

Presence and activation of pro-inflammatory macrophages are associated with CRYAB expression in vitro and after peripheral nerve injury.

Publication date: Mar 24, 2021

Inflammation constitutes both positive and negative aspects to recovery following peripheral nerve injury. Following damage to the peripheral nervous system (PNS), immune cells such as macrophages play a beneficial role in creating a supportive environment for regrowing axons by phagocytosing myelin and axonal debris. However, a prolonged inflammatory response after peripheral nerve injury has been implicated in the pathogenesis of negative symptoms like neuropathic pain. Therefore, the post-injury inflammation must be carefully controlled to prevent secondary damage while allowing for regeneration. CRYAB (also known as alphaB-crystallin/HSPB5) is a small heat shock protein that has many protective functions including an immunomodulatory role in mouse models of multiple sclerosis, spinal cord injury, and stroke. Because its expression wanes and rebounds in the early and late periods respectively after PNS damage, and CRYAB null mice with sciatic nerve crush injury display symptoms of pain, we investigated whether CRYAB is involved in the immune response following PNS injury. Sciatic nerve crush injuries were performed in age-matched Cryab knockout (Cryab) and wildtype (WT) female mice. Nerve segments distal to the injury site were processed by immunohistochemistry for macrophages and myelin while protein lysates of the nerves were analyzed for cytokines and chemokines using Luminex and enzyme-linked immunosorbent assay (ELISA). Peritoneal macrophages from the two genotypes were also cultured and polarized into pro-inflammatory or anti-inflammatory phenotypes where their supernatants were analyzed for cytokines and chemokines by ELISA and protein lysates for macrophage antigen presenting markers using western blotting. We report that (1) more pro-inflammatory CD16/32 macrophages are present in the nerves of Cryab mice at days 14 and 21 after sciatic nerve crush-injury compared to WT counterparts, and (2) CRYAB has an immunosuppressive effect on cytokine secretion [interleukin (IL)-β, IL-6, IL-12p40, tumor necrosis factor (TNF)-α] from pro-inflammatory macrophages in vitro. CRYAB may play a role in curbing the potentially detrimental pro-inflammatory macrophage response during the late stages of peripheral nerve regeneration.

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Concepts Keywords
Cytokines Pain
Immunohistochemistry Branches of biology
Immunomodulatory Immunology
Necrosis Cell biology
Neuropathic Immune system
Sclerosis Nerve injury
Tumor Neuroinflammation
Macrophage
Neuroregeneration
Myelin
Cytokine
Crystallin

Semantics

Type Source Name
disease MESH Inflammation
disease MESH neuropathic pain
disease MESH shock
disease MESH multiple sclerosis
disease MESH stroke
pathway REACTOME Reproduction
drug DRUGBANK Coenzyme M
disease MESH death
disease MESH neuroma
drug DRUGBANK Water
drug DRUGBANK Ketamine
drug DRUGBANK Xylazine
drug DRUGBANK Sucrose
drug DRUGBANK Pentaerythritol tetranitrate
drug DRUGBANK Ademetionine
drug DRUGBANK Ranitidine
drug DRUGBANK Tromethamine
drug DRUGBANK Glycerin
drug DRUGBANK Sodium metavanadate
disease MESH tics
drug DRUGBANK Aspartame
drug DRUGBANK Ibuprofen
drug DRUGBANK Filgrastim
drug DRUGBANK L-Glutamine
drug DRUGBANK Edetic Acid
drug DRUGBANK Isoxaflutole
drug DRUGBANK Proline

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