Increased plasma levels of epithelial neutrophil-activating peptide 78/CXCL5 during the remission of Neuromyelitis optica

BMC Neurology, Jul 2016

Background In neuromyelitis optica (NMO), one of the underlying pathogenic mechanisms is the formation of antigen-antibody complexes which can trigger an inflammatory response by inducing the infiltration of neutrophils in lesions. Epithelial neutrophil-activating peptide 78 (ENA 78), known as Chemokine (C-X-C motif) ligand 5 (CXCL5), belongs to the ELR-CXCL family. It recruits and activates neutrophils. The aim of this study was to evaluate ENA 78, IL-1β and TNF-α plasma levels in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. Methods ENA 78, IL-1β and TNF-α plasma levels were detected in 20 healthy controls (HC), 25 MS and 25 NMO patients using MILLIPLEX® map Human High Sensitivity Cytokine/Chemokine Panels. Results Plasma levels of ENA 78 were significantly higher in NMO patients than in HC (P < 0.001) and MS patients (P < 0.05). The NMO patients showed higher plasma levels of IL-1β compared with HC (P < 0.01). Further, increased plasma levels of TNF-α were found in the MS (P < 0.05) and NMO patients (P < 0.001). In addition, NMO patients had higher Expanded Disability Status Scale (EDSS) scores compared with MS patients (P < 0.05). EDSS scores were correlated with plasma levels of ENA 78 in NMO patients (P < 0.05). There were no significant correlations between EDSS scores and plasma levels of ENA 78 in MS patients (P > 0.05). Conclusions The overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α during the remission of NMO activates ENA 78, which in turn leads to neutrophil infiltration in lesions. ENA 78 plasma levels were correlated with EDSS scores in NMO patients. Elevated secretion of ENA 78 may be a critical step in neutrophil recruitment during the remission of NMO.

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Increased plasma levels of epithelial neutrophil-activating peptide 78/CXCL5 during the remission of Neuromyelitis optica

Yang et al. BMC Neurology Increased plasma levels of epithelial neutrophil-activating peptide 78/CXCL5 during the remission of Neuromyelitis optica Tao Yang 0 3 Su Wang 2 Qi Zheng 1 4 Lei Wang 4 Qian Li 0 3 Mingyan Wei 0 3 Zongpan Du 0 3 Yongping Fan 0 3 0 Department of Traditional Chinese Medicine, Beijing Tiantan Hospital, Capital Medical University , Beijing 100050 , People's Republic of China 1 Department of oncology, Guang An Men Hospital of China Academy of Chinese Medical Sciences , Beijing 100053 , People's Republic of China 2 Department of Oncology, Hiser Medical Center of Qingdao , Qingdao 266034 , People's Republic of China 3 Department of Traditional Chinese Medicine, Beijing Tiantan Hospital, Capital Medical University , Beijing 100050 , People's Republic of China 4 School of Traditional Chinese Medicine, Capital Medical University , Beijing 100050 , People's Republic of China Background: In neuromyelitis optica (NMO), one of the underlying pathogenic mechanisms is the formation of antigen-antibody complexes which can trigger an inflammatory response by inducing the infiltration of neutrophils in lesions. Epithelial neutrophil-activating peptide 78 (ENA 78), known as Chemokine (C-X-C motif) ligand 5 (CXCL5), belongs to the ELR-CXCL family. It recruits and activates neutrophils. The aim of this study was to evaluate ENA 78, IL-1β and TNF-α plasma levels in multiple sclerosis (MS) and neuromyelitis optica (NMO) patients. Methods: ENA 78, IL-1β and TNF-α plasma levels were detected in 20 healthy controls (HC), 25 MS and 25 NMO patients using MILLIPLEX® map Human High Sensitivity Cytokine/Chemokine Panels. Results: Plasma levels of ENA 78 were significantly higher in NMO patients than in HC (P < 0.001) and MS patients (P < 0.05). The NMO patients showed higher plasma levels of IL-1β compared with HC (P < 0.01). Further, increased plasma levels of TNF-α were found in the MS (P < 0.05) and NMO patients (P < 0.001). In addition, NMO patients had higher Expanded Disability Status Scale (EDSS) scores compared with MS patients (P < 0.05). EDSS scores were correlated with plasma levels of ENA 78 in NMO patients (P < 0.05). There were no significant correlations between EDSS scores and plasma levels of ENA 78 in MS patients (P > 0.05). Conclusions: The overproduction of pro-inflammatory cytokines such as IL-1β and TNF-α during the remission of NMO activates ENA 78, which in turn leads to neutrophil infiltration in lesions. ENA 78 plasma levels were correlated with EDSS scores in NMO patients. Elevated secretion of ENA 78 may be a critical step in neutrophil recruitment during the remission of NMO. Neuromyelitis optica; Epithelial neutrophil-activating peptide 78; Interleukin 1β; Tumor necrosis factor α Background Neuromyelitis optica (NMO, Devic’s syndrome) and multiple sclerosis (MS) are autoimmune and degenerative diseases characterized by demyelination of central nervous system (CNS), potentially leading to paralysis and other clinical symptoms [ 1–4 ]. NMO and MS are two of the most common diseases causing neurological disability in young adults [ 1, 5, 6 ]. Accumulating evidence has shown that NMO pathogenesis differs from MS, including aquaporin 4 (AQP4)-IgG increase and infiltration of granulocytes and macrophages [ 7, 8 ]. A significant feature distinguishing NMO from MS is the relatively higher number of neutrophils, eosinophils, macrophages and fewer T cells in the lesions [ 2, 8, 9 ]. Abnormal neutrophil aggregation in the lesions and increased AQP4-IgG are the notable features distinguishing NMO from MS [ 8, 10 ]. Neutrophil protease inhibition reduces AQP4-IgG damage in the mouse brain, which suggests that neutrophils play an important role in NMO pathology [7]. Studies also suggest a tight regulation of neutrophils and immune cell recruitment in NMO [ 2 ]. The innate immune response is orchestrated by inflammatory cells as a cascade of events, and each stage is associated with inflammatory cell recruitment and infiltration. Neutrophil infiltration is triggered by epithelial neutrophil-activating peptide 78 (ENA 78), which plays a role in tissue repair, metabolism, microbial killing, and angiogenesis [ 11, 12 ]. ENA 78 is a member of CXC chemokines, which enhance leukocyte recruitment and activation in autoimmune disorders and inflammatory diseases [ 13–15 ]. Its aberrant expression has been detected in rheumatoid arthritis, psoriasis, autism, bacterial meningitis, etc. [ 16–20 ]. ENA 78 is categorized into sub-classes based on the sequence and function, and characterized by the ELR (glutamic acid-leucinearginine) motif preceding the N-terminal Cys and activating C-X-C chemokine receptor type (CXCR) 2 selectively [21]. ENA 78 as a potent ELR+ CXC chemokine attracts and activates polymorphonuclear leukocytes (PMNLs) which are higher in patients with infections, inasmuch as the PMNLs are among the first cells to exist the peripheral blood and migrate to the inflammatory (...truncated)


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Tao Yang, Su Wang, Qi Zheng, Lei Wang, Qian Li, Mingyan Wei, Zongpan Du, Yongping Fan. Increased plasma levels of epithelial neutrophil-activating peptide 78/CXCL5 during the remission of Neuromyelitis optica, BMC Neurology, 2016, pp. 96, 16, DOI: 10.1186/s12883-016-0622-3