Comparison of disease‐modifying anti‐rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats

Hallak, Mohamad; Inal, Ahmet; Baktir, Mehmet Akif; Atasever, Ayhan

doi:10.1111/1440-1681.13906

Cited by 3 publications

References 37 publications

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Evidence of Silencing of Intestinal Inflammatory and Immune Transcripts Following Induction of Joint Inflammation

Moran,

Li,

Shen

et al. 2024

Preprint

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Disrupted intestinal epithelial barrier function has been proposed to be integral to rheumatoid arthritis (RA) progression and pathogenesis. To further define the molecular pathways in synovial inflammation and a response of the intestinal tissues, we have now used a rat model of mono-joint inflammatory arthritis, induced by intra-articular injection (IAI) of Complete Freunds adjuvant (CFA). The predominant inflammatory response of a single injection of the adjuvant into the knee joint resulted in rapid and reproducible formation of a fibrotic myeloid-infiltrated synovial pannus. Our aim was to determine how intestinal tissues, including the proximal and distal ileum and distal colon, respond to inflammatory changes in the synovium in a temporally coordinated manner by comparing their transcriptomic landscapes using RNASeq analyses. We confirmed the timeline of joint inflammation by knee joint swelling measurement, synovial fluid levels of the acute phase protein Inter-α-trypsin inhibitor heavy chains (ITIH) and demonstrated a self-correcting response of trabecular and cortical bone to the CFA challenge. Intestine-specific responses were monitored by 16S microbiome amplicon sequencing, histopathology for mucus layer integrity, and immune cell immunohistochemistry. We present data showing that the intestinal tissue response to the acute joint inflammation was region specific, with the ileum primarily responding with increased mucus secretion and silencing of T cell specific pathways, whereas the colon showed a transient upregulation of macrophages, with a broader suppression of immune related and metabolic pathway related transcripts. However, at no time after CFA-IAI were there significant changes in the fecal microbiome composition of the ileum or the colon. In summary, our data report for the first time a suppression of intestinal inflammatory and immune responses following the induction of joint inflammation and only minimal and transient changes in the microbiome.

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Evidence of Silencing of Intestinal Inflammatory and Immune Transcripts Following Induction of Joint Inflammation

Moran,

Li,

Shen

et al. 2024

Preprint

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The role of hypoxic microenvironment in autoimmune diseases

Gong,

Yang,

Wang

et al. 2024

Front. Immunol.

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The hypoxic microenvironment, characterized by significantly reduced oxygen levels within tissues, has emerged as a critical factor in the pathogenesis and progression of various autoimmune diseases (AIDs). Central to this process is the hypoxia-inducible factor-1 (HIF-1), which orchestrates a wide array of cellular responses under low oxygen conditions. This review delves into the multifaceted roles of the hypoxic microenvironment in modulating immune cell function, particularly highlighting its impact on immune activation, metabolic reprogramming, and angiogenesis. Specific focus is given to the mechanisms by which hypoxia contributes to the development and exacerbation of diseases such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), multiple sclerosis (MS), and dermatomyositis (DM). In these conditions, the hypoxic microenvironment not only disrupts immune tolerance but also enhances inflammatory responses and promotes tissue damage. The review also discusses emerging therapeutic strategies aimed at targeting the hypoxic pathways, including the application of HIF-1α inhibitors, mTOR inhibitors, and other modulators of the hypoxic response. By providing a comprehensive overview of the interplay between hypoxia and immune dysfunction in AIDs, this review offers new perspectives on the underlying mechanisms of these diseases and highlights potential avenues for therapeutic intervention.

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Using Hybrid Nanoplatforms to Combine Traditional Anti-Inflammatory Drug Delivery with RNA-Based Therapeutics for Macrophage Reprograming

Almeida,

Miranda,

Reis

et al. 2024

IJMS

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There is growing evidence on the significant role of prolonged inflammation in triggering and progressing of numerous diseases with substantial health and socioeconomic impacts, such as musculoskeletal, cardiovascular and autoimmune disorders, and cancer. Therefore, there is an urgent need to develop therapies that can overcome the main challenges of currently used approaches, such as non-target action, partial modulation of the complex inflammatory pathways, and short-term effects, to effectively manage and resolve chronic inflammatory states. This work investigates the therapeutic synergy of clinically relevant anti-inflammatory agents approaching naïve and classically activated macrophages owing to their central role in inflammation. Aiming at human therapies, a dual-loading nanoplatform reunites molecules with different physico-chemical properties in a single system, seeking to more effectively and comprehensively regulate macrophage functions for precision cell guidance and greater versatility in disease managing. To build this platform, palmitic acid grafted chitosan, superparamagnetic iron oxide nanoparticles, the clinically approved NSAID celecoxib (also known as Celebrex®), and RNA technologies were combined into superparamagnetic polymeric micelles (SPMs). Our findings demonstrated that traditional anti-inflammatory drugs such as celecoxib and microRNA molecules were efficiently delivered by the SPMs, altering the inflammatory profile of naïve (M0φ) and M1-primed macrophages (M1φ) assessed by gene and protein expression. The impact of the dual-loaded SPMs in naïve Mφ is an interesting finding towards the modulation of the initial immune response, reducing the potential for chronic inflammation and promoting tissue healing. Collectively, these encouraging results demonstrate the promise of multi-nanomedicine strategies to enhance the efficacy of therapeutic interventions by offering a fresh approach to more precisely and carefully regulated nanotherapeutics delivery.

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Comparison of disease‐modifying anti‐rheumatic drugs and hyperbaric oxygen therapy in the experimental model of rheumatoid arthritis in rats

Cited by 3 publications

References 37 publications

Evidence of Silencing of Intestinal Inflammatory and Immune Transcripts Following Induction of Joint Inflammation

Evidence of Silencing of Intestinal Inflammatory and Immune Transcripts Following Induction of Joint Inflammation

The role of hypoxic microenvironment in autoimmune diseases

Using Hybrid Nanoplatforms to Combine Traditional Anti-Inflammatory Drug Delivery with RNA-Based Therapeutics for Macrophage Reprograming

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