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)