Cem Gabay

Bio: Cem Gabay is an academic researcher from Anschutz Medical Campus. The author has contributed to research in topics: Messenger RNA & Inflammation. The author has an hindex of 7, co-authored 8 publications receiving 6212 citations.

Acute-Phase Proteins and Other Systemic Responses to Inflammation

Abstract: A large number of changes, distant from the site or sites of inflammation and involving many organ systems, may accompany inflammation. In 1930 interest was focused on these changes by the discovery of C-reactive protein (so named because it reacted with the pneumococcal C-polysaccharide) in the plasma of patients during the acute phase of pneumococcal pneumonia.1 Accordingly, these systemic changes have since been referred to as the acute-phase response,2 even though they accompany both acute and chronic inflammatory disorders. New acute-phase phenomena continue to be recognized, and the mechanisms mediating them are becoming better understood. This review summarizes much of . . .

Leptin deficiency enhances sensitivity to endotoxin-induced lethality

Abstract: Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. Se...

Mouse IL-1 receptor antagonist isoforms: complementary DNA cloning and protein expression of intracellular isoform and tissue distribution of secreted and intracellular IL-1 receptor antagonist in vivo.

Abstract: IL-1R antagonist (IL-1Ra) is a competitive inhibitor of the binding of IL-1 to IL-1R. IL-1Ra refers to two different proteins derived from the same gene by alternate splicing of two different first exons. One protein contains a leader sequence and is secreted (sIL-1Ra), whereas the other remains intracellular (icIL-1Ra). We describe the cloning of mouse icIL-1Ra cDNA, the expression of the recombinant mouse icIL-1Ra protein, and the tissue distribution of sIL-1Ra and icIL-1Ra mRNA and of icIL-1Ra protein in control and LPS-injected mice. As described in the human and the rabbit, mouse icIL-1Ra protein differs from mature mouse sIL-1Ra protein by seven amino acids at the amino terminus. In addition, human and mouse icIL-1Ra are 77% identical. Regulation of IL-1Ra isoforms was examined in normal mice and after LPS injection. Circulating levels were undetectable in control mice, but were strongly increased 4 h after LPS injection. Using a ribonuclease protection assay (RPA), we found that icIL-1Ra mRNA was expressed constitutively in skin and in LPS-stimulated RAW 264.7 murine macrophages. Consistent with the RNA studies, Western blot analysis showed that murine icIL-1Ra protein was constitutively expressed in skin and in LPS-stimulated RAW 264.7 cells. In contrast, sIL-1Ra mRNA was not detected by RPA in tissues of control mice, but was strongly up-regulated in the lung, spleen, and liver after LPS injection. Using RPA, primer extension assay and 5' rapid amplification of cDNA ends, we were able to demonstrate the presence of different transcription start sites for murine sIL-1Ra mRNA.

Treatment of Rheumatoid Arthritis With IL-1 Inhibitors

Abstract: Extensive evidence from both in vivo and in vitro experiments indicate that IL-1, a prototypic proinflammatory cytokine, is involved in the mechanisms that lead to progressive joint destruction in RA. IL-1Ra, a member of the IL-1 family, binds IL-1 receptors but does not induce any cellular responses. IL-1Ra competitively inhibits the binding of IL-1 to its cell surface receptors and thus, acts as an endogenous anti-inflammatory mediator. However, the results of several studies suggest that a relatively deficient production in IL- 1Ra as compared to that of IL-1 in RA synovium may pre-dispose to the perpetuation of chronic inflammation. Systemic administration of IL-1Ra, or local delivery into the joints by gene therapy, in different experimental animal models of arthritis attenuated the severity of the inflammatory response and reduced articular destruction. In addition, treatment of rheumatoid patients with IL-1Ra led to an improvement in different clinical and biological parameters and to a reduction in the radiological signs of joint erosions. Encouraging results also have been reported in both in vitro and in vivo experimental animal models of arthritis through using other strategies designed to block the effects of IL-1 at the level of production, prevent the binding of IL-1 to its cell surface receptors, or interfere with the effects of IL-1 at the post-receptor level.

Adipose tissue, adipokines, and inflammation.

Abstract: White adipose tissue is no longer considered an inert tissue mainly devoted to energy storage but is emerging as an active participant in regulating physiologic and pathologic processes, including immunity and inflammation. Macrophages are components of adipose tissue and actively participate in its activities. Furthermore, cross-talk between lymphocytes and adipocytes can lead to immune regulation. Adipose tissue produces and releases a variety of proinflammatory and anti-inflammatory factors, including the adipokines leptin, adiponectin, resistin, and visfatin, as well as cytokines and chemokines, such as TNF-α, IL-6, monocyte chemoattractant protein 1, and others. Proinflammatory molecules produced by adipose tissue have been implicated as active participants in the development of insulin resistance and the increased risk of cardiovascular disease associated with obesity. In contrast, reduced leptin levels might predispose to increased susceptibility to infection caused by reduced T-cell responses in malnourished individuals. Altered adipokine levels have been observed in a variety of inflammatory conditions, although their pathogenic role has not been completely clarified.

Associations of Depression With C-Reactive Protein, IL-1, and IL-6 : A Meta-Analysis

Abstract: Objective:To assess the magnitude and direction of associations of depression with C-reactive protein (CRP), interleukin (IL)-1, and IL-6 in community and clinical samples.Methods:Systematic review of articles published between January 1967 and January 2008 in the PubMed and PsycINFO electronic data

Adipokines: inflammation and the pleiotropic role of white adipose tissue.

Abstract: White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name 'adipocytokines' or 'adipokines'. However, since most are neither 'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFalpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.

Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis

Abstract: Background: Individuals with chronic obstructive pulmonary disease (COPD) are at increased risk of cardiovascular diseases, osteoporosis, and muscle wasting. Systemic inflammation may be involved in the pathogenesis of these disorders. A study was undertaken to determine whether systemic inflammation is present in stable COPD. Methods: A systematic review was conducted of studies which reported on the relationship between COPD, forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC), and levels of various systemic inflammatory markers: C-reactive protein (CRP), fibrinogen, leucocytes, tumour necrosis factor-a (TNF-a), and interleukins 6 and 8. Where possible the results were pooled together to produce a summary estimate using a random or fixed effects model. Results: Fourteen original studies were identified. Overall, the standardised mean difference in the CRP level between COPD and control subjects was 0.53 units (95% confidence interval (CI) 0.34 to 0.72). The standardised mean difference in the fibrinogen level was 0.47 units (95% CI 0.29 to 0.65). Circulating leucocytes were also higher in COPD than in control subjects (standardised mean difference 0.44 units (95% CI 0.20 to 0.67)), as were serum TNF-a levels (standardised mean difference 0.59 units (95% CI 0.29 to 0.89)). Conclusions: Reduced lung function is associated with increased levels of systemic inflammatory markers which may have important pathophysiological and therapeutic implications for subjects with stable COPD.