Spleen: A new role for an old player?

Tarantino, Giovanni; Savastano, Silvia; Capone, Domênico; Colao, Annamaria

doi:10.3748/wjg.v17.i33.3776

Cited by 98 publications

(62 citation statements)

References 53 publications

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“…61 Fig . 2E shows an enlargement of the spleen size for mice after MWCNT treatment for 14 days, indicative of the occurrence of splenomegaly, compared to untreated mice.…”

Section: 28mentioning

confidence: 99%

Carbon nanotubes stimulate synovial inflammation by inducing systemic pro-inflammatory cytokines

et al. 2016

Nanoscale

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a Carbon nanotubes (CNTs) have promising applications in a wide range of biomedical fields, including imaging, drug/gene delivery and other therapeutics; however, the biosafety concerns of CNTs should be addressed. To date, many reports have documented the toxicological effects on the cells, tissue or organs that are in direct contact with the tubes; however, there is limited evidence to unravel the secondary toxicity upon CNT treatment. Moreover, more effort is needed to gain a definitive understanding of the adverse outcome pathway (AOP) for CNTs, and a pragmatic framework for risk assessment has not been established yet. In the current study, we aimed to decipher the secondary toxicity to joints under CNT exposure. We demonstrated that carboxylated multi-wall CNTs (MWCNTs-COOH) significantly provoked systemic pro-inflammatory responses, leading to synovial inflammation within knee joints, as evidenced by the infiltration of pro-inflammatory cells in the synovium and meniscus. Mechanistic studies showed that MWCNTs-COOH stimulated pro-inflammatory effects by activating macrophages, and the secreted pro-inflammatory cytokines primed the synoviocytes and chondrocytes, resulting in enhanced production of a large array of enzymes involved in articular cartilage degeneration, including matrix metalloproteinase (MMP) members and cyclooxygenase (COX) members, and increased enzymatic activity of MMPs was demonstrated. Blockade of the cytokines by antibodies significantly attenuated the production of these enzymes. Our current study thus suggests that there is a novel secondary toxicity of CNTs, namely a new AOP to understand the indirect effects of carbon nanotubes: synovial inflammation due to the alteration of the priming state of synoviocytes and chondrocytes under CNT-induced systemic inflammatory conditions.

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“…61 Fig . 2E shows an enlargement of the spleen size for mice after MWCNT treatment for 14 days, indicative of the occurrence of splenomegaly, compared to untreated mice.…”

Section: 28mentioning

confidence: 99%

Carbon nanotubes stimulate synovial inflammation by inducing systemic pro-inflammatory cytokines

et al. 2016

Nanoscale

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“…Several alterations in the immune system occur in the obese state in humans and rodents, including splenic-immune dysfunctions [10]. For instance, alterations in the spleen volume (as a stable index of chronic inflammation) alongside activation of the immune system and elevated concentration of high sensitivity C-reactive protein (CRP), characterize young adult obese subjects with non-alcoholic fatty liver disease [11,12]. Thus, it is possible that immune and/or metabolic responses originating in the spleen are involved in obesity and T2D development.…”

Section: Introductionmentioning

confidence: 99%

Splenectomy attenuates obesity and decreases insulin hypersecretion in hypothalamic obese rats

et al. 2015

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“…The main cause of immunosuppression is lymphocytic apoptosis [3][4][5]. About one fourth of the body's lymphocytes are stored in spleen, which is vital in regulating the immune function and initiating immune responses [6,7]. Lymphocytes in spleen are activated when presented with exogenous chemicals; these activated lymphocytes are sensitive to signals that lead to apoptosis [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

cAMP/PKA Signaling Pathway Induces Apoptosis by Inhibited NF-κB in Aluminum Chloride-Treated Lymphocytes In Vitro

Wang

Cao

et al. 2015

Biol Trace Elem Res

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To explore the apoptosis mechanism in lymphocytes of rats induced by aluminum chloride (AlCl3) by activating cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway, the splenic lymphocytes of rats were cultured and exposed to different concentrations of AlCl3 for 24 h. The final concentrations of AlCl3 (AlCl3 · 6H2O) in supernatant were 0 (control group, CG), 0.3 mmol/L (low-dose group, LG), 0.6 mmol/L (mid-dose group, MG), and 1.2 mmol/L (high-dose group, HG), respectively. Lymphocytes Apoptosis rate, intracellular cAMP content, PKA, survivin, B cell lymphoma/leukemia-2 (Bcl-2) and Bcl-2-associated X protein (Bax) mRNA expressions, and the mRNA and protein expressions of nuclear factor-κ-gene binding (NF-κB, p65) were detected, respectively. The results showed that apoptosis index of lymphocytes, cAMP content in intracellular and PKA mRNA expression were significantly upregulated, whereas NF-κB and survivin mRNA expressions, nuclear NF-κB (p65) protein expression, and the ratio of Bcl-2 and Bax mRNA expression were downregulated in the AlCl3-treated groups compared with those in CG. The results indicated that the activated cAMP/PKA signaling pathway induces apoptosis by inhibited NF-κB in AlCl3-treated lymphocytes in vitro.

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Spleen: A new role for an old player?

Cited by 98 publications

References 53 publications

Carbon nanotubes stimulate synovial inflammation by inducing systemic pro-inflammatory cytokines

Carbon nanotubes stimulate synovial inflammation by inducing systemic pro-inflammatory cytokines

Splenectomy attenuates obesity and decreases insulin hypersecretion in hypothalamic obese rats

cAMP/PKA Signaling Pathway Induces Apoptosis by Inhibited NF-κB in Aluminum Chloride-Treated Lymphocytes In Vitro

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