Sarcoidosis exosomes stimulate monocytes to produce pro-inflammatory cytokines and CCL2
SCIENTIFIC REPORTS
Authors: Wahlund, Casper J. E.; Akpinar, Gozde Gucluler; Steiner, Loic; Ibrahim, Ahmed; Bandeira, Elga; Lepzien, Rico; Lukic, Ana; Smed-Sorensen, Anna; Kullberg, Susanna; Eklund, Anders; Grunewald, Johan; Gabrielsson, Susanne
Abstract
Pulmonary sarcoidosis has unknown etiology, a difficult diagnostic procedure and no curative treatment. Extracellular vesicles including exosomes are nano-sized entities released from all cell types. Previous studies of exosomes from bronchoalveolar lavage fluid (BALF) of sarcoidosis patients have revealed pro-inflammatory components and abilities, but cell sources and mechanisms have not been identified. In the current study, we found that BALF exosomes from sarcoidosis patients, but not from healthy individuals, induced a dose-dependent elevation of intracellular IL-1 beta in monocytes. Analyses of supernatants showed that patient exosomes also induced release of IL-1 beta, IL-6 and TNF from both PBMCs and enriched monocytes, suggesting that the observed effect is direct on monocytes. The potently chemotactic chemokine CCL2 was induced by exosomes from a subgroup of patients, and in a blocking assay the exosome-induced CCL2 was reduced for 13 out of 19 patients by the asthma drug Montelukast, a cysteinyl leukotriene receptor antagonist. Further, reactive oxygen species generation by PBMCs was induced to a higher degree by patient exosomes compared to healthy exosomes. These findings add to an emerging picture of exosomes as mediators and disseminators of inflammation, and open for further investigations of the link between CCL2 and exosomal leukotrienes in sarcoidosis.
Blockage of C-C Chemokine Ligand 2 Alleviated the Appendicitis-Induced Injury in Rabbit Model
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH
Authors: Liu, Wen; Zeng, Anrong; Tang, Hanzhou; Qiang, JinWei
Abstract
C-C chemokine ligand 2 (CCL2), a low-molecular-weight cytokine, is upregulated in inflammation-related diseases. However, the underlying function of CCL2 remains unknown in human appendicitis. The present study aimed to examine the role of CCL2 in appendicitis. An enzyme-linked immunosorbent assay was performed to examine the secretion of CCL2 in the peripheral blood of patients with simple and complex appendicitis, respectively. A flow cytometry assay was used to quantify the level of the CCL2 receptor, CCR2. Moreover, we constructed an appendicitis model in rabbits. Quantitative real time-polymerase chain reaction and Western blot were used to determine CCL2 and CCR2 levels in the appendicitis model. CCL2 antibodies were used to silence the endogenous activity of CCL2in vivo.Magnetic resonance imaging and a histopathology assay were used to examine the appendicitis-induced injury in rabbits. Our results suggested that CCL2 and its main receptor CCR2 were upregulated in patients with appendicitis, particularly those with complex appendicitis (gangrenous and perforated appendicitis). Moreover, CCL2 silencing alleviated the appendicitis-induced injury in rabbits. Our findings not only illustrate the potential value of CCL2 as a biomarker in appendicitis diagnosing but also provide novel insight into appendicitis treatment.