Chemotherapeutic agent CPT-11 eliminates peritoneal resident macrophages by inducing apoptosis

Huang, Mei-Yun; Pan, Hao; Liang, Yaxuan; Wei, Hongxia; Xu, Lihui; Zha, Qing-Bing; He, Xian-Hui; Ouyang, Dong-Yun

doi:10.1007/s10495-015-1193-2

Cited by 4 publications

(9 citation statements)

References 31 publications

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“…However, the numbers of SPMs were not significantly changed by CPT-11, despite their increased ratios within the CD11b + population (Figures 1 B,C). Together with previous studies ( 13 ), these results indicated that the resident peritoneal macrophages were rapidly depleted by i.p. CPT-11 treatment.…”

Section: Resultssupporting

confidence: 89%

“…Although we have demonstrated that CPT-11 can deplete the resident peritoneal macrophages ( 13 ), the dynamic details underlying this process remain unknown. For example, could the resident peritoneal macrophages and B1 cells recover from CPT-11 treatment by self-renewal?…”

Section: Introductionmentioning

confidence: 99%

“…Previously, we have reported that CPT-11, a chemotherapeutic agent, can eliminate resident peritoneal macrophages by inducing apoptosis ( 13 ). CPT-11 is a first-line drug used in clinic to treat colorectal cancer and small cell lung cancer ( 14 ).…”

Section: Introductionmentioning

confidence: 99%

“…Beyond its direct toxicity to the intestinal epithelial cells, it has also been shown to activate inflammasomes and IL-1β secretion through Janus N-terminal kinase and nuclear factor-κB signaling ( 20 ). Consequently, CPT-11 treatment may induce colitis as dextran sodium sulfate does ( 13 , 20 ). In addition, CPT-11 may induce hyper-proliferation of mesenteric lymph node cells and hyper-production of inflammatory cytokines from them upon mitogen stimulation ( 21 ).…”

Section: Introductionmentioning

confidence: 99%

“…Indeed, CPT-11 treatment increases infiltration of macrophages and secretion of chemokines (including monocyte chemotactic protein 1) in tumor-bearing mice ( 26 ), when compared with vehicle treatment. Moreover, elimination of the peritoneal resident macrophages by CPT-11 ( 13 ) may impair the homeostasis of gastrointestinal immunity and thus weaken its actions against intestinal cancers.…”

Section: Introductionmentioning

confidence: 99%

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Prolonged Deleterious Influences of Chemotherapeutic Agent CPT-11 on Resident Peritoneal Macrophages and B1 Cells

Bai

Zhang

et al. 2018

Front. Immunol.

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CPT-11 is a first-line chemotherapeutic agent for the treatment of colorectal cancer in clinic. Previous studies including ours have demonstrated that CPT-11 is, however, toxic to the intestinal epithelium and resident peritoneal macrophages. By interacting with B1 cells, the resident peritoneal macrophages play critical roles in the maintenance of gastrointestinal homeostasis. It remains therefore elusive whether these peritoneal innate immune cells could be rebuilt spontaneously or artificially after being impaired by CPT-11 administration. In this study, we found that mouse resident peritoneal macrophages, namely the large peritoneal macrophages (LPMs) with a CD11b+F4/80hiGATA6+ phenotype, and B1 (CD19+CD23−) cells were depleted by intraperitoneal (i.p.) CPT-11 treatment within 1 week, but reappeared from day 14 after CPT-11 treatment. However, the recovery processes of these innate immune cells were slow, as their counts could not be fully recovered even 2 months later, when compared with that of vehicle-treated control group. Interestingly, in the peritoneal cavity of the mice treated with CPT-11, the cell counts of LPMs and B1 cells were significantly increased after adoptive transfer with syngeneic peritoneal exudate cells (PECs) from healthy mice. Adoptive transfer with bone marrow cells also slightly increased, although not significantly, the cell counts of LPMs and B1 cells in CPT-11-treated mice. The survival rate of bacterial infected mice was significantly reduced by i.p. CPT-11 treatment in comparison with vehicle-treated or untreated control groups. Besides, oral administration of CPT-11 also had a delayed toxicity on the resident peritoneal macrophages. Our results suggest that CPT-11 has prolonged deleterious effects on peritoneal innate immune cells but adoptive transfer with PECs may accelerate their recovery processes, highlighting the potential of adoptive cell transfer as an avenue to counteract the adverse effects of this chemotherapeutic agent.

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Section: Resultssupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Prolonged Deleterious Influences of Chemotherapeutic Agent CPT-11 on Resident Peritoneal Macrophages and B1 Cells

Bai

Zhang

et al. 2018

Front. Immunol.

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Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis

et al. 2020

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Objectives Wedelolactone exhibits regulatory effects on some inflammatory diseases. However, the anti‐inflammatory mechanism of wedelolactone has not been entirely unravelled. Therefore, the present study focuses on investigating the mechanism of wedelolactone on NLRP3 inflammasome in macrophages and its influence on MSU‐induced inflammation. Materials and Methods BMDM, J774A.1 and PMA‐differentiated THP‐1 macrophages were primed with LPS and then stimulated with ATP or nigericin or MSU crystal in the presence or absence of wedelolactone. The cell lysates and supernatants were collected to detect NLRP3 inflammasome components such as NLRP3, ASC and caspase 1, as well as pyroptosis and IL‐1β production. In addition, the anti‐inflammatory effects of wedelolactone on MSU‐induced peritonitis and arthritis mice were also evaluated. Results We found that wedelolactone broadly inhibited NLRP3 inflammasome activation and pyroptosis and IL‐1β secretion. Wedelolactone also block ASC oligomerization and speck formation. The inhibitory effects of wedelolactone were abrogated by PKA inhibitor H89, which also attenuated wedelolactone‐enhanced Ser/Thr phosphorylation of NLRP3 at PKA‐specific sites. Importantly, wedelolactone could abate MSU‐induced IL‐1β production and neutrophils migration into peritoneal cavity, and reduced caspase 1 (p20) and IL‐1β expression in the joint tissue of MSU‐induced arthritis. Conclusion Our results indicate that wedelolactone promotes the Ser/Thr phosphorylation of NLRP3 to inhibit inflammasome activation and pyroptosis partly through potentiating PKA signalling, thus identifying its potential use for treating MSU‐induced peritonitis and gouty arthritis.

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Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes

Liu¹,

Li²,

Pen³

et al. 2022

BioMed Eng OnLine

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Background CPT-11 (irinotecan) is one of the most efficient agents used for colorectal cancer chemotherapy. However, as for many other chemotherapeutic drugs, how to minimize the side effects of CPT-11 still needs to be thoroughly described. Objectives This study aimed to develop the CPT-11-loaded DSPE-PEG 2000 targeting EGFR liposomal delivery system and characterize its targeting specificity and therapeutic effect on colorectal cancer (CRC) cells in vitro and in vivo. Results The synthesized liposome exhibited spherical shapes (84.6 ± 1.2 nm to 150.4 nm ± 0.8 nm of estimated average sizes), good stability, sustained release, and enough drug loading (55.19%). For in vitro experiments, SW620 cells treated with CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome showed lower survival extended level of intracellular ROS production. In addition, it generated an enhanced apoptotic cell rate by upregulating the protein expression of both cleaved-caspase-3 and cleaved-caspase-9 compared with those of SW620 cells treated with free CPT-11. Importantly, the xenograft model showed that both the non-target and EGFR-targeted liposomes significantly inhibited tumor growth compared to free CPT-11. Conclusions Compared with the non-target CPT-11-loaded DSPE-PEG2000 liposome, CPT-11-loaded DSPE-PEG2000 targeting EGFR liposome treatment showed much better antitumor activity in vitro in vivo. Thus, our findings provide new assets and expectations for CRC targeting therapy.

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Chemotherapeutic agent CPT-11 eliminates peritoneal resident macrophages by inducing apoptosis

Cited by 4 publications

References 31 publications

Prolonged Deleterious Influences of Chemotherapeutic Agent CPT-11 on Resident Peritoneal Macrophages and B1 Cells

Prolonged Deleterious Influences of Chemotherapeutic Agent CPT-11 on Resident Peritoneal Macrophages and B1 Cells

Wedelolactone facilitates Ser/Thr phosphorylation of NLRP3 dependent on PKA signalling to block inflammasome activation and pyroptosis

Targeted delivery of irinotecan to colon cancer cells using epidermal growth factor receptor-conjugated liposomes

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